Sunday, April 26, 2020

Be Kind to Cancer Patients

If someone who works for you (or with you) is diagnosed with cancer, please be considerate of the emotions he or she is going through. I was just thinking back to when I was diagnosed with lung cancer and what it was like to go to work. It was not like anything I ever experienced emotionally. A cancer diagnosis will consume every waking moment. I've heard people say that they throw themselves into their work to keep their mind off of what is happening in their personal life. That sounds great but it's not reality for many people like me.

I remember the call from my doctor when he told me I have a tumor in my lung and that I needed to come see him. I also remember going to work the next day (and several days and weeks after) and how hard it was for me to concentrate on my job responsibilities. When you are told that you have cancer, your life is turned upside down and nothing else seems to matter but your life, and your family. In my case a wife and 3 young boys ages 5, 3 and 1. It literally consumed my thoughts and it was very hard to separate that from what is in front of me. After all, if you think you may die, you are thinking of those you will leave behind. A deadline at the office now seems less important. Not that it's an excuse, because work needs to get done and in my case I managed to get it done. I'm only suggesting that in the mind of the cancer patient, it's really hard to separate the work from the personal. I don't believe showing empathy is hard to do. Why not be kind and try to put yourself in the other shoes? 

From my personal experience, showing a lack of empathy to people who are dealing with a life threatening or life-changing diagnosis can be devastating to the person affected. Consider receiving news that your son has Fragile X and may never speak. Or news that your daughter is blind and may never see. Or news that you have cancer and may not live to see your next birthday. Then going to work and having your boss act as if nothing is going on, being tone deaf to what you are going through emotionally. Work still must be done and the world doesn't stop because of a serious diagnosis. But if you are that boss, or co-worker, I hope you will be considerate and think about what it would be like if you received that news.

#KindnessMatters #Gratitude

Thursday, December 26, 2019

Betting On Great Researchers

Have you ever met someone that just gives you a sense of confidence that anything is possible? I've met many researchers over the years and some of them just fill me with such hope that I feel that given the funding necessary to advance their ideas, a breakthrough would happen. I don't say this naively to suggest that it's just about money. Because I know that money doesn't solve all problems and in research there is no sure bet. But in medical research, often times good ideas stay in the minds of scientists due to lack of sufficient resources to do the experiments that could make huge advancements in understanding disease. And with some researchers you can just tell that they have ideas in their head that given the sufficient support there would be huge return. Researchers like Dr. Rudolf Jaenisch.

I have recently come to know Rudolf Jaenisch, a Founding Member of Whitehead Institute at MIT and National Medal of Science recipient. His lab caught my attention when I read this article about how one of his postdoctoral fellows, Shawn Liu "restored activity to the fragile X syndrome gene in affected neurons using a modified CRISPR/Cas9 system they developed that removes the methylation—the molecular tags that keep the mutant gene shut off—suggesting that this method may prove to be a useful paradigm for targeting diseases caused by abnormal methylation." So I decided to contact Dr. Jaenisch and went to meet with him and Shawn Liu. And wow was I impressed with both of them and how they were on to something big!

But what really struck me was that Shawn had developed this tool and he thought Fragile X was the perfect target to test it on, but the lab had no direct funding for Fragile X research. They were able to support this one project and got positive results, but now to take this discovery and move it forward will require more experiments. Bottom line, it will require more money. And without financial support, this line of experimentation will not move forward. Dr. Jaenisch described CRISPR as a tool, but that more work is needed to to tell it what to do. In other words, a promising discovery was made to prove a hunch but how sad it will be if this line of research ends here. He also described how long it would take to get an National Institutes of Health (NIH) grant, but that with smaller increments of funding he could pursue his theory. And that could lead to a larger NIH grant. I've always said this is why disease foundations and philanthropists play such a critical role in funding research.

On a recent visit with Dr. Jaenisch he shared more of his research vision and his passion was contagious. He spoke about collaboration and how big breakthroughs require insights from different areas of research such as biological engineering. For example his eyes lit up when he described how amazing it would be if his friend and colleague Bob Langer at Koch Institute at MIT brought his perspective. I could tell that Dr. Jaenisch really had a road map of what he thought was possible in Fragile X research. And collaboration of different disciplines could bring answers to some of the mysteries that still exist. This is also why I believe places like Boston and Cambridge are so special - there is such a cluster of academic research labs and biotech companies that make if fertile ground for research and development of treatments to help patients. But Dr. Jaenisch, as renowned as he is, still can't bring his Fragile X research to the next level without adequate funding. It would be such a lost opportunity.

Of course this is just another example of similar conversations I've had with cancer researchers like Johnathan Whetstine and so many others. Most people don't know that researchers do not get automatic funding from the institutions where they work. Even places like MIT and Massachusetts General Hospital. Each lab is responsible for it's own funding and has to apply for grants from government sources like NIH or from private sources like FRAXA Research Foundation. The good news is that all of us are fortunate that there are people like Rudolf Jaenisch and Johnathan Whetstine who go to work every day with determination and commitment. I just wish more people could get to know them. Hey, even though I don't fully understand epigenetics or CRISPR I am grateful to know the ones that do!

#research #gratitude

Sunday, September 15, 2019

FRAXA Biotech Games™. It Could Only Happen In Boston

Three years ago, I had this crazy idea that I would organize an event in Boston that would bring together the Boston biotech community to network in a friendly setting, form new relationships and potential collaborations, while raising money for research in Boston area labs. I found several people who shared my vision and together we launched FRAXA Biotech Games™. The theme is “we’re all in this together," and the beneficiary is FRAXA Research Foundation, which funds Fragile X research around the world. This event supports research in Boston Bear Lab at Picower Institute at MIT, and the Jeannie Lee Lab at Harvard/MGH. FRAXA's mission is to find effective treatments and ultimately a cure for Fragile X, the most common inherited cause of autism and learning disabilities. FRAXA collaborates with these Boston research institutions and also biotech companies such as Ovid Therapeutics.

On September 12, 2019 over 300 people from the biotech community gathered at Cambridge Crossing for our second gathering - a "friendly" competition in a series of back yard lawn games like cornhole and Kanjam. It was amazing to see my vision come to life. The mix of scientists from biotech companies like Takeda and Ginkgo Bioworks, research labs like Feng Lab at McGovern Institute at MIT, and people from companies like Morgan Stanley and Aldevron that supply products and services to the biotech industry was a perfect blend of dedicated professionals that should get to know each other better. Since I truly believe that we are all in this together to make a difference in the lives of patients around the world, this is a perfect theme for this event. This community in Boston is the home to innovation, so it is also the perfect place to convene this interesting collection of people.

Greater Boston is home to almost 1,000 biotechnology companies ranging from small start-ups to billion-dollar pharmaceutical companies. Scores of universities in the area feed the region a vast network of scientists. Several top life science venture capital firms such as Third Rock Ventures and incubators like Lab Central and Johnson and Johnson Innovation support this innovative community. It is arguably the nation’s biotechnology nerve center and hoe to innovation! And home to Bob Socci, voice of the New England Patriots, who was in the house! Thank you for being our emcee Bob.

And I believe in serendipity. By bringing together this innovation community – companies, investors, scientists, academic labs and advocates – we are increasing the chance that the right people will meet to spark that big idea. The more people we bring to Fragile X the better our chance of a breakthrough in treatments and ultimately a cure for Fragile X.

Stay tuned for more as we roll out more events to promote collaboration in Boston's biotech community. And thank you to my volunteer organizing committee, Kendall Square Association for being a community partner and Cambridge Crossing for hosting the event. And special thanks to Katie Clapp, co-founder of FRAXA for allowing me to bring this idea to FRAXA, and Keith Spiro Media, for providing media services and for believing in my ability to connect people.

Oh and the winner?!! My friends at Synlogic Therapeutics. A worthy champion. #gratitude #research

Saturday, June 15, 2019

It's Not (Just) About The Money: It's About The People

As I reflect on my work with pharmaceutical and biotech companies over the past twenty years, I realize I have seen a lot. My experience spans many aspects of the industry and I've met hundreds of people along the way. The people I've worked with include product (brand) marketing, public relations, market research (competitive analysis), medical education, reimbursement, patient advocacy, and research and development. I also worked with a lot of people in the nonprofit patient advocacy sector who relied on the pharma industry for funding for important education programs. And when I sent to work for one of these nonprofit cancer research organizations, I had the opportunity to meet many academic researchers who had collaborative relationships with industry. All of this led me to become an evangelist for medical research and work in the nonprofit sector and work with scientists in academic labs. So I have a good understanding of the people in the ecosystem of drug development. I have an opportunity to share my experience and stories about these people who have crossed my path. From large companies like Novartis, small companies like Fulcrum Therapeutics, and scientists in academic labs, I've worked with a lot of committed people who are not in it (just) for the money. I will be writing about some of these amazing people in the coming months.

Read the headlines today about the pharmaceutical industry and the one word I see over and over is greed. I get why people are upset. Americans spend about $1,200 on prescriptions drugs a year, according to the latest figures from the Organization for Economic Cooperation and Development. That’s more than people pay in any other developed country in the world.  And yes, we've all read the stories about price hikes and guys like "Pharma Bro" Martin Shkreli—famously known as the guy that jacked up the price of a lifesaving AIDS treatment by 5,000%. I don't propose to have the answer to solving the problem of high prescription drug costs. But I have a perspective from working with the industry for many years, and it's unfair to call everyone in pharma and biotech "greedy." I'm here to tell you they are not. In fact, my experience is with mostly good people who are like me, trying to make a difference in improving the lives of people with life-threatening disease like cancer, and rare disorders such as Fragile X syndrome.

And consider that developing a new prescription medicine that gains marketing approval is estimated to cost drug makers $2.6 billion according to a recent study by Tufts Center for the Study of Drug Development and published in the Journal of Health Economics. And the average time it takes to bring a drug through clinical trials averages over 10 years. Maybe most importantly, nearly 9 out of 10 drugs fail along the way. So that means companies invest billions knowing that the chance of success is narrow. So, if you or a loved one has a life-threatening condition or complex rare disease, think about the process of what it takes to bring a new discovery to patients. Time, money, risk, commitment, collaboration. It doesn't just happen. And it certainly doesn't happen overnight. So the cost of treatments is clearly a major problem in the United States. My goal is not to solve that problem. Rather, I want to introduce people to some of the dedicated people I've met along the way in my journey to be an evangelist for medical research..

Thursday, March 14, 2019

Meet Ellen Skala: Super Advocate

I was in Washington, D.C. recently on Capitol Hill meeting with my representatives in Congress to advocate for federal funding for biomedical research. As I’ve written many times, I believe government agencies like National Institutes of Health (NIH), National Cancer Institute (NCI) and Department of Defense (DoD) play a critical role in advancing science and making discoveries that impact millions of lives. As a lung cancer survivor, I’ve advocated for cancer research for many years. This time I was on the hill on behalf of the organization I work for, FRAXA Research Foundation, advocating for Fragile X research on Advocacy Day, an event organized by the National Fragile X Foundation. And I met an advocate that inspired me and reinforced my long-held belief that one person can make a difference. Meet Ellen Skala.

Ellen Skala, also referred to as Elle, was on Capitol Hill to advocate that day too. I had spoken with her several times, but I had never met her in person. She contacted FRAXA in August 2018 about creating a personal fundraising campaign for research, so I was excited about her interest in supporting our mission. What I didn’t know at the time was just how remarkable this young woman is. Elle had set a goal to raise $10,000 for Fragile X research by her birthday. Her plan was to reach out to her family and friends, share the story about her friendship with Ryan Pitcher, and advocate for Fragile X families and individuals. On top of that, she committed to shaving her head if she met her fundraising goal. 

Ryan Pitcher has Fragile X syndrome. Elle met Ryan over a year ago, and as she describes it, “he has changed my life in the most beautiful of ways.” What stood out most to her was his huge heart. She was amazed by how deeply he cares about his inner circle of family and friends, always wanting to make sure they are happy and taken care of. Elle wanted people to know about him. In her words, “we all could use a little bit more of that care and compassion in our lives, so out of my passion for the Fragile X Community, I am creating this fundraiser.” After meeting Elle, what stood out most to me was her huge heart. She volunteers her time, raising awareness and advocating for government funding, and led her own personal fundraising campaign. So, just as she said she wanted people to know about Ryan, I wanted people to know about her.

She set out last fall to share Ryan’s story and ask for donations to FRAXA in support of our mission. Those who know her understood just how important Ryan and his family are to her, and gladly supported her fundraiser. She explained why Fragile X research was so important to her personally and the difference their gifts would make. Elle also reached out to Fragile X families in the DC area, where she has recently relocated, to hear their stories and connection to Fragile X. She quickly became a Fragile X advocate in the area and shared FRAXA’s mission with everyone she met. Elle grew up in the Midwest, and after graduating from the University of Missouri – Columbia, moved to Washington, DC in the summer of 2018 to start a full-time job. Everyone who has met Elle has come to learn what her friends and family already knew. She is passionate, relentless, and has a burning desire to create a positive impact on the lives of others.

On February 9, 2019, Elle celebrated her 23rd birthday in New York with Ryan and his family. She surpassed her goal, raising $10,611 for Fragile X research. Wow! And true to her word she shaved her head completely bald. Elle shared with us that her hair has always been a huge part of her identity. As she explains, “It has helped distinguish me from other people. Seriously, my grandmother could find me in a crowd because of my hair. Just like my hair is a part of my identity, Fragile X is a part of Ryan’s.” Elle’s commitment to the Fragile X community and to research is truly inspiring. I’m sure her members of Congress were equally as inspired by meeting her. She proves that one person can make a difference. To me she is a super advocate.

#gratitude #advocate #research #compassion

Friday, January 25, 2019

Celebrating Innovation!

I went to a really unique event called Celebrating Innovation! last night at the Center for the Arts at the Armory in Somerville, MA. The event was produced by The Story Collider and featured personal stories from 5 people who work in the life sciences industry in Boston/Cambridge. I was interested in attending because the show was sponsored by Blueprint Medicines, a Cambridge biotech company I follow that designs and develops precision therapies, including multiple programs for genomically defined cancers (including lung cancer), rare diseases and cancer immunotherapy.

What I found unique about the program was that it was an opportunity for five individuals with deep commitment to science to share something personal with the audience, most who are also involved in the scientific community. The audience got a glimpse of each of the storyteller's lives outside the lab, and outside of the business of biotech. There they were, on a stage, under the lights with only a microphone, forming a bond with about 100 strangers. And we all felt a connection to them because we share a passion for research and discovery, and we wanted to know a little about what makes these people tick. I found it to be inspiring.

Not only do I believe that Boston is a center of innovation in research and development, it attracts brilliant and interesting people from around the world. Alexis Borisy, a partner at venture firm Third Rock Ventures, as well as a co-founder and board member of Blueprint Medicines, told stories about his journey to being a builder of businesses, starting with how he spent time in the lab with his dad, a scientist, as early as 7 years old. Before the show started, he told me about his first job selling peanuts at the Wisconsin Badgers football games at age 14. He's from Madison, WI so being from Minnesota myself, we had a few laughs about life in the Midwest back in the day. It was nice to see a personal side of a man who has 20 years of experience building and operating innovative science-based organizations.

Likewise, Bob Coughlin, President and CEO of Massachusetts Biotechnology Council (MassBio) told the story of his journey to being a leading voice representing the life sciences industry in Massachusetts. He told of how he moved from politics as a state rep of a district encompassing his hometown of Dedham, MA to getting involved with Cystic Fibrosis (CF). He had volunteered to help raise money for the Cystic Fibrosis Foundation to help friends who had kids with CF, and in fact serving as honorary chairman of the CF Foundation's Great Strides Walk in Dedham since 1995. When his son was born in 2002 with CF, he talked about how it hit home with his family. And he's come to appreciate how long it takes to develop new drugs to treat diseases like CF. But he ended by praising the efforts of the biotech industry and the hard work and dedication involved in developing new treatments.

I came away from the event with a renewed sense of appreciation for the work of the thousands of people who work in the biotech industry in greater Boston. And getting a peek into the personal lives of some of these people was pretty special. Companies like Blueprint Medicines, the sponsor of the event, are made up of very talented hard-working people (3 of whom also told their stories) who truly believe their work will make a difference in the lives of so many people affected by cancer, cystic fibrosis and hundreds of other diseases and disorders. I am grateful that I was invited to attend this special program and look forward to writing more about Blueprint Medicines and other biotech companies in Boston and Cambridge. These companies, and the academic research institutions that spawn many of them as startups, make our region a world-class hub of medical research and innovation. Sometimes it's nice to gather in a different setting to celebrate innovation.

#biotech #cancer #research

Thursday, October 4, 2018

Putting More Runners in the Race

When I heard that Dr. Jim Allison won the Nobel Prize the other day, it hit me that for breakthroughs in medical research to happen, we need to have as many runners in the race as possible. It makes sense right? The more scientists we have in the field researching cancer the better chance we have that one (or more) of those researchers in the lab will hit on an idea that will lead to more advanced studies. And the more new studies undertaken by labs - the more runners in the race - the closer we get to having real breakthrough treatments get to patients. Just like in a marathon - the more runners who train and qualify for the race, the more who are likely to cross the finish line.

In fragile X, FRAXA Research Foundation has been putting more runners into the race for many years. In early years there was not much known about fragile X. So FRAXA poured millions of dollars into basic research at labs around the world. The idea was that the more brilliant minds in the laboratory we have working on unlocking mysteries of fragile X, the better the chance that one - or more - of these labs will discover something that will move the science forward. Many of these FRAXA funded postdocs published successful research, moved on to start their own labs and brought their own postdocs into the field - more runners in the race!

By identifying many new treatment pathways through lab studies in mice and fruit flies, FRAXA moved the science forward by funding research that matched potential drugs to treat those pathways in clinical trials. Some researchers used the results of FRAXA funded small clinical trials to go to larger funding sources like the National Institutes of Health (NIH) and the Department of Defense - more runners in the race!

And in recent years, FRAXA has built partnerships with pharmaceutical and biotech companies that have brought more smart minds and technologies to the field of fragile X research. FRAXA supports a mouse facility that companies can access to test their drugs for potential in fragile X. The FRAXA Drug Validation Initiative (FRAXA-DVI) provides speedy, cost-effective, objective testing of potential new Fragile X treatments. FRAXA has funded FRAXA-DVI every year since 2011. There are several examples of young startup companies who have tested their compounds in FRAXA fragile X mice and seen positive results. These companies then can take the data from these tests to start their own clinical studies. More runners in the race!

One example is Tetra Discovery Partners, a startup biotech company that has a drug they are studying in Alzheimer's Disease. Tetra had a hunch that it might work in fragile X, so they tested their drug in the FRAXA-DVI and had positive results. The data was used to get approval for a Phase 2 study of BPN14770 as a potential treatment for Fragile X Syndrome. BPN14770 has also received Orphan Drug Designation from the U.S. Food and Drug Agency for the treatment of Fragile X Syndrome. And the clinical trial is being run by a world class fragile X researcher at Rush University in Chicago, Elizabeth Berry-Kravis, MD, PhD. And FRAXA is funding this trial! More superstar runners in the race!

This is why we need to keep supporting medical research. It takes the federal government, philanthropy and industry all working to support more brilliant minds and ideas. Only by continuing to put more runners in the race will we find effective treatments and ultimately cures for diseases and disorders like cancer and fragile X.

#Cancer #Research #fragileX #Gratitude

Monday, October 1, 2018

Medical Research Takes Time

I often write about the need for funding for cancer research. In order for breakthroughs to occur, researchers need to fund their labs to test their theories. Dr. Jim Allison, from the University of Texas MD Anderson Cancer Center is one of those researchers whose work over many decades was recognized today with the 2018 Nobel Prize in Physiology or Medicine for launching an effective new way to attack cancer by treating the immune system rather than the tumor.

Dr. Allison started his research career at MD Anderson in 1977. Trust me when I tell you that he was an early pioneer in immunotherapy. When I met Dr. Allison in 2014 he was just starting to get recognition for his important work. So what we take for granted today - that treatments for cancer include unleashing the body's own immune system to fight cancer - started decades ago. This is why we need to consistently fund research over time. We never know when that next breakthrough will occur.

This is not just true in cancer research. In my day job, I have been raising funds for fragile X research for the past year and a half at FRAXA Research Foundation. Fragile X is the most common inherited cause of autism and learning disabilities. It's a complicated neurological disorder that will require a lot more research funding to make breakthroughs like Dr. Allison's in cancer. But I believe it will happen if we continue to put resources into the labs that study fragile X.

And breakthroughs require funding of basic research to begin with. "We still have a lot to learn ... we need to continue to fund basic research because that's where this came from," Allison said in his news conference today. "The big jumps come of the basic science and we need to keep that in mind."

I am honored to have met so many brilliant researchers like Dr. Jim Allison. And I will continue to advocate for research funding. We are all in this together. #PrecisionMedicine #Immunotherapy #NobelPrize

Sunday, August 26, 2018

Tone Deaf on Lung Cancer

I have been involved in cancer research and advocacy for many years. I try to never disparage any cancer advocacy groups that raise money to fund research and other programs to help cancer patients and their families. We're all in this together. However, the American Cancer Society (ACS) came out with a recent survey asking "What cancer issues do you care about most? I was so disappointed that lung cancer was not even mentioned as an issue! Here is the survey:

My lung cancer diagnosis was in 1998, and I had a positive outcome - no spread to lymph nodes, no chemotherapy - and my lobectomy was difficult but a small price to pay. And I have lived a life of gratitude ever since, so I don't enjoy being critical of cancer organizations that have a role to play. I just get tired of the stigma attached to lung cancer as a smokers disease and when the ACS put out this survey, it totally played right into the stigma. According to the ACS's own statistics, nearly 160,000 Americans die from lung cancer each year - by far the leading cancer killer. And up to 20% of those never smoked - again according to the ACS! That means up to over 30,000 non-smokers die of lung cancer. Wow.

How then is it possible for the ACS to put out a survey asking about what cancer issues we care about and not even have lung cancer as one of the issues??? The survey includes breast cancer and colorectal cancer among others. But the questions mentioned in the survey that are related to lung cancer in their view are "Global tobacco issues" and "Smoke-free restaurants and workplaces" and "Tax on tobacco products." Doesn't this play into the stigma of lung cancer being a "smokers disease?" This is not acceptable.  More Americans die from lung cancer than breast, colorectal and prostate cancer combined! So yes, lung cancer is an issue I care about - but the ACS apparently doesn't think it ranks among the 13 issues of importance in their survey. Give me a break.

There is a lot of chatter on social media right now about this. We as a community are not happy. I haven't seen any logical response from the ACS to date. Frankly, I'm getting tired of feeling like I'm shouting into the wind about this. When will large organizations like the American Cancer Society realize that they are responsible for continuing to promote the stigma about lung cancer as a smoking issue. Anyone with lungs can get lung cancer. It's time to end the stigma, and time for the ACS to start acting responsibly.

Tuesday, April 24, 2018

Blending Art With Science

On April 7, 2018 over 100 people gathered at Boston Children’s Hospital for a special conference called Success Strategies for Individuals and Families Impacted by Fragile X. It was an inspirational day that included presentations by 2 fragile X researchers, Dr. Craig Erickson from Cincinnati Children’s Hospital, and Dr. Carol Wilkinson from Boston Children’s Hospital. Both researchers are funded by FRAXA Research Foundation, the platinum sponsor of the conference. I am Director of Community Relations for FRAXA, and I invited my friend and artist, Maria Castellano-Usery to join us for the day.

Maria started Brushstrokes With Impact™, a campaign where she merges art, community, and raising money for causes she feels strongly about. Over the course of twenty-eight “Paint-a-Thon” events (which have taken place in Maine, Massachusetts, New Hampshire, and New York) she has raised money for many good causes. At the conference she set up her easel at the FRAXA table and spent the day creating an 8”x8” painting that was given at the end of the conference to the winner of a raffle. Maria was well received by the fragile X community. So many people stopped by to watch and it was a unique experience of combining art with science. FRAXA’s mission is to find effective treatments and a cure for fragile X, the most common inherited cause of learning disabilities and autism. FRAXA invests money directly into research labs around the world.

The winner of the raffle was Cliff Lamb. His daughter Nicole was diagnosed with fragile X at Yale in 2017. Nicole is 9 years old. He and his wife Katherine have another daughter Natalie (12 years old) who was also tested but is not a carrier of fragile X. Cliff says, “Nicole loves the painting, especially the colors and the texture of the cloth.” She takes it off the wall to play like a toy, so Cliff needs to make sure she does not damage this work of art. Nicole is always searching for sensory input and she is very sensitive to background noise. Cliff knows going forward he needs to help her as she experiences sensory overload in places where background noise is high. Cliff is an electrical engineer and he spends much time analyzing the spectral analysis of background noise and ways to mitigate. Maria’s painting could not have found a better home! And FRAXA found some new friends.

Thursday, March 1, 2018

A Bowl of Gratitude

I was introduced recently to Lynne Sarnoff-Christensen by her cousin, and my friend Jeffrey Cohen. You see, she makes pottery and well, more specifically she make “bowls of gratitude”. So of course, Jeffrey knew that I would hit it off with Lynne because he knows I live a life full of gratitude. Another friend, Keith Spiro said I just had to buy a bowl – so I did. The idea is to put notes in the bowl about things you are grateful for. So it’s my new thing. I’ve long been a fan of Shawn Achor and I’ve gotten into the habit of writing down things that I am grateful for. So this bowl of gratitude will be where I put my notes. And I will encourage my family to also add their notes to the bowl. We have a tradition on Thanksgiving to go around the table before we dig in to our meal, to share what we are thankful for. We shouldn’t just do this at Thanksgiving!

When I called Lynne, she explained her philosophy and I get it: “You didn’t get from there to here without people believing in you. Gratitude…I got a bowlful! Do You?” And of course, she is from my home state of Minnesota, which made it even more fun. Bottom line is that I do live a life full of gratitude. I’m a cancer survivor, so what more to be grateful for than going through that experience and still being here. But more than that, it’s about my family – my wife and my 3 boys – and my close circle of friends. And my colleagues at work, and the families that we help give hope by supporting biomedical research. It’s still my passion to advocate for funding for cancer research. It’s also my passion to advocate for fragile X research. Fragile X is the most common inherited cause of autism and intellectual disabilities.

                                             Me with Jeffrey in Arizona

Becoming part of the fragile X community through my work at FRAXA Research Foundation has taught me a lot about gratitude. There but for the grace of God go I, that I do not have children with disabilities. Yes I had a difficult lung cancer experience years ago, but I have met so many families with children with fragile X who face significant challenges – different than my cancer journey. It’s a lifetime of caring for children and worrying about what will happen to them when the parents are gone. It’s made me a better person being involved in the fragile X community. And it’s another reason I am grateful. So thank you, Jeffrey Cohen, for introducing me to Lynne. And thank you for allowing me to become part of your family. I’ve enjoyed getting to know Arlene, Josh and Alli. Here’s a fist bump to you Josh!


Wednesday, February 14, 2018

My Biomedical Research Advocacy Continues

I have often written about the need for adequate research funding and the challenge researchers have funding their labs. The cancer researchers that I met over the past 4 years consistently told me they spend up to 75% of their time fundraising - between writing grants to the National Institues of Health (NIH), private foundations and public charities, and meeting with individual donors. Scientists like John Whetstine at Massachusetts General Hospital happily meet with people to talk about their research and John works a lot of hours writing grants. The more time he spends in his lab the less time he has to test new ideas. Another scientist, Dr. Wayne Marasco at Dana-Farber Cancer Institute laments the fact that he could be in the lab making discoveries were it not for the fact that he has to spend so much time writing grants. And in oncology, the chance of receiving an NIH grant is only 10%. Having now spent almost a year at FRAXA Research Foundation, I see that it is no different in research labs that study fragile X and other neurological disorders.

FRAXA has poured over $26 million into fragile X research, funding research projects across many different laboratories and in 2017 funded some exciting projects such as drug repurposing, clinical trials and gene reactivation. These labs could do so much more if they had the resources. However, as with cancer research, fragile X scientists have the same challenge in securing funding. The time it takes to write grants to the NIH or Department of Defense (DoD) takes up an inordinate amount of time. This is so frustrating to me because many labs have theories that could be studied if time could be freed up from work outside of the lab. Of course, it also points out the important role that organizations like FRAXA play. FRAXA funding helps support post docs in the labs to test the theories of primary investigators as well as their own hypotheses. A $50,000 grant from FRAXA can support one post doc for a year, which is a huge benefit to a laboratory. FRAXA has supported many post docs over the years and many have then made discoveries that led them to moving on to start their own labs. This opens a space to bring in new post docs into the field. For example, FRAXA has supported Dr. Mark Bear at Massachusetts Institute of Technology (MIT) for many years. Several post docs from his lab have since moved to open their own labs. A great example of this is Dr. Kimberly Huber, who started her own lab at UT Southwestern. Over time, this means that more brilliant scientists are brought in to the field of fragile X research. Without FRAXA’s support, this would not be possible. Another important role that FRAXA has played historically is de-risking research. By funding early basic and translational research, FRAXA has helped several labs use the data produced from FRAXA grants to apply for and receive NIH grants. For example, FRAXA funded Dr. Hongbing Wang’s lab and this lead to a large NIH grant.

The United States still leads the world in biomedical research spending but other countries are closing the gap. From 2007-2012 the U.S. share of global public and private biomedical R&D investments dropped from 51 to 45 percent, while a generation ago the U.S. funded as much as 80 percent of the global activity. Meanwhile, many Asian countries raised their investments in the same period with double-digit annual growth rates, topped by China's nearly 33 percent. This is concerning to me. I think we will see the negative impact of this 20 years from now. The breakthroughs we see today were paid for by research 20 years ago. The fact that the amount of research funded by the NIH declined by nearly 25% between 2003 and 2015 is a huge hit to research, and in particular to researchers starting out in their careers (post docs). Therefore, I believe we need the government to up the ante on public sector research funding, and private philanthropy must continue to play an important role. This is why I continue to be an evangelist and advocate for biomedical research funding.

Tuesday, February 6, 2018

Why I joined FRAXA Research Foundation

In 2017, I joined FRAXA Research Foundation, a national nonprofit in Newburyport, MA as Director of Development and Community Relations. FRAXA’s mission is to find effective treatments and a cure for fragile X, the most common inherited cause of autism and intellectual disabilities. I had spent the previous 17 years in cancer education and research, most recently as Vice President of Development at the National Foundation for Cancer Research (NFCR) in Bethesda, MD.

While fragile X research was a departure from cancer, I was drawn to FRAXA firstly because of the mission focus on research. The model of funding individual research labs across many different institutions was similar to how NFCR approached researcher: accept proposals from several labs, vet them through a rigorous scientific review process, and select the most promising projects. FRAXA has been putting over $1 million into fragile X research since its inception in 1994, over $26 million to date. Another reason I joined FRAXA was the people, particularly the founders Katie Clapp and Dr. Mike Tranfaglia. They are parents of a son with fragile X, and have shown a relentless commitment to funding biomedical research for more than 23 years. Once I met a few board members, I was sold. Each of the members of the board of directors is a parent and they all tirelessly give their time. All of them commit to raising money for FRAXA – a lot of money. This impressed me so much, because I had not seen that level of fundraising commitment at previous organizations. 

I have also come to understand that while fragile X is a rare neurological disease, some of the research is similar to work in cancer, such as CRISPR and epigenetics. In fact, some of the researchers I knew in cancer research are colleagues of fragile X researchers. That was cool to find out and made me realize what a small world it is. The level of commitment is the common thread too – all of the researchers I have met along my journey are truly passionate about their work. I really love my new job because I can continue to be the #CancerResearchEvangelist and can continue to support medical research in my day job too. In addition, I don’t have to commute to Washington, D.C. from my home near Boston.


Sunday, August 27, 2017

A Leader in Innovation

Let me tell you about one of the most passionate, committed cancer researchers I have ever met. I actually first met Johnathan Whetstine on Twitter, in January of 2016. He started following me and I started following him because we seemed to share and like similar content and points of view on Twitter. The common theme was the need to support basic cancer research. At the time I was working for the National Foundation for Cancer Research and my role was to raise money to support cancer research laboratories like Johnathan’s. After a series of exchanges during the spring on Twitter, he asked me if I was going to the Partners Healthcare World Medical Innovation Forum in Boston. I told him I was, and we planned to meet there. What I didn’t know until I got there, was that Johnathan was actually one of the presenters! Turns out he was to be onstage when they revealed the “Disruptive Dozen.” The Disruptive Dozen was created to identify and rank the most disruptive technologies that Partners Healthcare’s leading faculty feel will break through over the next decade in cancer care. Wow! His work in epigenetics was one of the promising technologies, and Johnathan’s lab was leading the way. I had no idea that I had met one of the most accomplished researchers in the cancer research community!


Johnathan and I became fast friends because he shared my passion for research, and he was bursting with excitement about his work. He told me he knew he wanted to become a scientist when he was 14 years old because he was inspired by a science teacher who made science fun and interesting. Growing up in rural Kentucky and Tennessee he had huge ambitions and decided in high school that he wanted to find a cure for cancer. And he ended up as a post-doctoral fellow in the lab of Dr. Yang Shi at Harvard Medical School before getting his own lab. He’s a Ph.D. so he doesn’t treat patients, but he hopes his work will provide insights into the development of better molecular diagnostics, epigenetic therapeutic molecules, or novel therapeutic combinations so better efficacy can be achieved in treating cancer. Research like Johnathan’s also are the foundation in the research continuum: basic research discoveries need to take place to technologies into development, and lead to clinical trials. This is the first step in getting a new drug or technology from bench to bedside.


According to Johnathan, he spends up to 75% of his time on fundraising for his lab. This includes writing NIH grants and grants to the American Cancer Society, American Lung Association and foundations. He has built some strong relationships with these organizations. He also has connected with many patients through this process, attending events and inviting interested parties to his lab. However, it seems to me he should be spending 75% of his time in the lab – imagine how much more impact he could have on advancing research if he didn’t have to spend so much time on paperwork? He would love to add more postdocs to his lab to do additional experiments based on his theories, but he has to balance that with his sources of funding. He is responsible for funding his lab. It’s like running a small business because he has to make decisions on growth and staffing based on the revenue coming in. He laments how challenging and how many years it takes to get an NIH R01 grant, the largest grants. The average age of first-time R01 funded investigators who have Ph.D. is 42 and the average grant is $499,221. Are we missing out on research discoveries from younger scientists because of a lack of funding? Scientists like Johnathan love to have people visit his lab so he can share his work and hopefully inspire people support him, but the unfortunate reality is that this takes up a tremendous amount of his time. 

Thursday, June 29, 2017

The Role of Basic Research in Precision Medicine


Me and Johnathan outside his lab in Charlestown, MA

I had the privilege of interviewing Johnathan Whetstine, a cancer researcher at Massachusetts General Hospital, at his laboratory to get his perspective on precision medicine. Johnathan’s field is cancer epigenetics. His lab investigates how the microenvionment around DNA controls gene expression while maintaining a stable genome. I thought he’d be the perfect person to give me historical context of precision medicine and what role basic scientific research plays in the process. “If you ask me as a basic scientist, the beauty of precision medicine is that you are starting to apply mechanistic knowledge in the context of how individuals will be diagnosed and treated.  By applying knowledge from laboratory settings, the medical community can make better decisions about what biomarkers to use as well as make predictions about the response,” said Johnathan.   He added, “By taking this approach, you’re now tailor-making a treatment to a person and cancer sub-type. This approach is in contrast to the one drug fits all policy.  Personalized Medicine is embracing individuals and cancer sub-types. Human variation in the population and the fact that tumors can change requires this in depth evaluation that will change medicine moving forward. The beauty of personalized medicine is it benefits from discovery!” Basic scientific labs like Johnathan’s are critical to the ecosystem as more targeted treatment of cancer evolves.


The example Johnathan likes to give to describe basic research and precision medicine is comparing an old car to a new car. He says, “If you open the hood of a ‘64 Chevy Impala you can see where all the parts are, it’s all connected so you can fix it – it’s very simple. New cars today are typically cased, all electronics, you can’t see what some of the parts are so it’s hard to figure out a problem. I can mechanistically see what’s inside the old car and the average mechanic can fix it. On the new car, the average mechanic can’t just pick it up and fix it because they don’t always understand the mechanism.”  So in other words, Johnathan thinks precision medicine is the process of starting to simplify and map a complex engine so better diagnosis and treatment can be made. Precision medicine is a combination of scientists and physicians building tools to understand what is ‘under the hood’ so treatment is more effective long term.” And he adds, “If you know more about what is inside the tumor, you can deliver more optimal therapy, you can go after cancer sub-types. Look at lung cancer obviously, between the ROS mutations and the translocations and various EGFR mutations, you can predict if someone is or isn’t going to fail on certain treatments. Why? Here’s the gene, here’s the information that’s biologically linked in the lab – that together gives you precision medicine.”

Me and Johnathan and our wives at the MGH 100 2016


Johnathan says he likes to remind people that the advances in precision medicine, and the breakthroughs in targeted treatments we have seen are a result of all of the investment in research that came before him.  In his words, “Something that was invested in 20 years ago doesn’t mean it’s not going to pay off today. A big example of this is sequencing. We take for granted that we can go to an office at Mass. General or other places, and they can take your tumor and tell you the gene(s) that are changed and possibly impacting tumor action and therapeutic options.  This exists because of the earlier investments both in the technology as well as the science to identify the genes that are important.” He’s referring to the investment into the Human Genome Project, and the impact genomics has had in the United States. Between 1988 and 2012, the federal government invested $14.5 billion in the field of genomics, with an enormous economic and societal impact from that investment. It’s estimated this returned $966 billion in economic impact in the United States, according to the advocacy group United for Medical Research. Johnathan added, “I would challenge anybody to answer the question, where can you make a $14.5 billion investment and turn it into a trillion dollars today?” And amazingly, while it took almost $15 billion and more than a decade for the government-funded DNA effort to fully sequence a human genome for the first time, companies can now sequence a whole genome for about $1,000 and do it in a day.


I asked Johnathan what he sees in the future for precision medicine. In his words, “I predict that the more we start to break apart various pathways in the cell that are involved with drug resistance, or pathways that are involved in certain therapeutic sensitivities, we’re going to find commonalities across tumors, and also tumor specific properties, which provides a collection of names to mark and develop drug targets.” He sees initiatives like the Cancer Center tumor profiling and MGH Biobank as important to the future of precision medicine. He thinks it’s great that everyone who walks in the door is asked if they want to contribute. Even John’s mom asks the question, “why would I want to do that?” He calls it putting your DNA in the game. In his words, “There have been something like 115 published studies using this biobank where they’ve established unique genetic relationships to disease to direct responses.”  He adds, “Let’s look at lung cancer. Some of the mutations are rare – as small as less than 1% - but when you have over 2 million people diagnosed across the spectrum, that’s a lot of people. The problem is that so many people are not connected. People need to empower themselves. If you live in an area with limited tools in America, you’re not required to get treated there. There are many big hospitals that want to help. You have to be your own advocate.”

Johnathan giving me a tour of his research lab


John believes that we must continue to fund basic cancer research so we can find more targeted treatments for more cancer patients. “Basic labs help put the narrative together – when you have the narrative then you have precision medicine. If I give you 2 nouns and ask you to write a story, you’re going to have to put it into context. We’re identifying nouns and by identifying them through sequencing and disease associations, you’re getting context.”, says Johnathan. He also believes it’s a generational thing. “Science is not just about today. Just as our children are the future of America, my protégés, the people who train with me are the future of this field. The cool thing is I now have my trainees going off to other institutions such as University of Colorado and Stanford, so it’s literally like a family tree – and that family tree has lasting impact. Each discovery gets seeded in a new location and we haven’t even touched the tip of the iceberg.” As for his advice to cancer patients, he says “I always recommend that you give yourself the power to go to places that have precision medicine as a focus. The best way to be empowered is to make sure this is a big focus of the institution – that gives it credibility. Go to trusted sources and get educated – get connected to people you can identify with.” 


Wednesday, May 17, 2017

Communication Between Cancer Patients and Researchers: Challenges and Opportunities

Taking The Mystery Out Of Cancer Research

When I started working at the National Foundation for Cancer Research, I was charged with educating our donors about the cancer research we were funding. To do that, I felt it would be helpful to meet the actual researchers personally, get to know them and their work, so that I could articulate this to our donors. What better way to take the mystery out of research by sharing their stories? I became known as the Cancer Research Evangelist because after getting to know many cancer researchers personally, and visiting their laboratories, I became an advocate for the need for funding to support their work.
In my experience, many of the researchers I met were passionate and approachable. They had offices with pictures of their families, they loved their work, and they just came across as real people. However, not a lot of people I know have ever met a cancer researcher.
I think it’s important that researchers and patients get to know each other because researchers can help give patients hope that someone is working on figuring out what is causing their cancer, and working on how to treat it. And I think it’s important for researchers to engage with patients because it puts a face on the disease their laboratory is trying to solve. This gives the researchers motivation and greater purpose to their work. I think there are a few important reasons for this, as well as challenges and opportunities to improve the communication between researchers and patients.
The Challenge For Researchers
In my experience, there are two primary reasons that researchers do not engage with patients, and the challenges for them are very understandable.
First, the system: researchers are so burdened with getting funding grants, and with making sure that they produce published papers so they get tenure, they simply do not have the time to engage with patients. Indeed, I was astonished to learn that the institutions where researchers worked did not financially support their labs. For example, if you’re a cancer researcher at Dana Farber, you get lab space but you are responsible for raising money to support your staff and some of the equipment and supplies. Almost every single researcher I’ve met has told me that they spend about 75% of their time fundraising. That’s how much time it takes to write grants to the NIH and nonprofits like the American Cancer Society and other foundations, do all the paperwork, and meet with foundations to help with fundraising. This all takes valuable time away from time spent in the laboratory. Given that, it’s hard to imagine researchers doing outreach to patients.
Unfortunately, this is the nature of the system, and I think that sometimes the humanity gets lost in the sense that hospitals or major medical research institutions may not appreciate the value of researchers spending time with patients and educating the public. From the researchers’ perspective, educating the public can help spread the word about their work and help in raising money for their work. Patients can become advocates for the research lab.
In a perfect world, research labs would operate on a fixed supported budget where they know they have money to do their work. And the time they may have wasted not getting a grant – which in oncology, only 12% of grants get funded – would be spent on community outreach and education.
In my opinion, the second reason many researchers don’t connect with patients may just be because of personality. The average researcher may not be very comfortable meeting with laypeople to talk about their work, or see the value in connecting with patients. While I’ve met some that are at ease in social settings, for some this is just not their gift.
The Challenge For Patients
How many cancer patients have ever met a cancer researcher? Or visited an actual research laboratory? Probably not very many. But I think patients would benefit by connecting with cancer researchers to understand what they do and see how committed they are to the cause. And they would have the ability to share their real patient experience.
In my experience, the primary reason patients don’t connect with researchers is they just don’t know how to find or approach a researcher. Before I started meeting researchers and visiting labs, I thought of cancer research as this vague, mysterious and institutional concept. I just thought of it as the institution — such as Dana Farber or Mayo Clinic — that was doing the research. I never even considered the actual people who were doing the work! Most patients probably are like I was, and didn’t even think about contacting real researchers. Other patients may just have a personality that makes them uncomfortable reaching out to strangers, or they might be intimidated by talking to someone with high level standing in the cancer community. In particular, many may not think they could be comfortable contacting someone at what they might consider prestigious institutions.
But patients could benefit from meeting researchers and advancing their understanding of their disease. What better source of information about a patient’s actual cancer diagnosis than a person doing research on the specific problem? Looking back at my own case, when I was diagnosed with a neuroendocrine tumor in my lung, it would have been amazing to meet a scientist who studies my disease.
The Opportunities
I believe there are many opportunities to improve the communication between researchers and patients, starting with these two:
First, cancer nonprofits and related organizations need to play a role in connecting patients to researchers. A good example is the American Association for Cancer Research Scientist-Survivor Program (AACR SSP). The goal of the program is to encourage survivor and patient advocates to develop stronger backgrounds in cancer research and related issues, keep abreast of recent advances, and be exposed to the knowledge and dedication of cancer scientists. It also allows for scientists to gain a more personal understanding of cancer’s impact on patients and their loved ones. Several of my Precision Medicine Advocates Program colleagues attended the 2017 AACR SSP and wrote about it here, here, and here.
Many cancer nonprofits such as the American Lung Association, and the Multiple Myeloma Research Foundation also have access to and have relationships with researchers. They may know which ones are open to and have the personality to want to meet patients. These nonprofits should proactively educate their communities and encourage them to ask to meet researchers. And they can invite researchers to their events. For example, last year at a Making Strides event, the American Cancer Society invited researcher Johnathan Whetstine from Massachusetts General Hospital to come meet participants in the walk. He volunteered his time to come out meet people. Hospitals and medical research organizations can also have “meet the researcher” events and encourage patients to come.
Second, social media is a great opportunity for patients to find researchers interested and willing to meet and engage with patients. For example, anyone can post asking if there is a scientist out there who is studying the particular area of interest who is willing to connect.  Researchers on social media are likely the ones already engaging with patients.

The bottom line is that some of the challenges such as researchers’ time cannot be solved. But with willingness from all stakeholders, and with the help of nonprofits and social media, the communication between researchers and patients can improve.


Wednesday, February 22, 2017

Community Building in the Age of Precision Medicine

When I was diagnosed with lung cancer years ago, my wife (who is a nurse) told me that the first thing I needed to do was to become my own advocate – to be proactive in seeking information about my disease and my care strategy. Of course, this was before the advent of genetic testing and the era of precision medicine. But even today, too many cancer patients die or suffer through toxic treatments and expensive hospitalizations when state of the art molecular testing could have offered better options with either approved treatments or promising clinical trials. Most patients are not as proactive and self-advocating as they could be, and there is a need to raise this awareness about just how a newly diagnosed patient can become his/her own advocate. One way is to connect with other patients with a similar diagnosis, either online or in person.

More and more cancer patients are attending medical conferences and connecting with other patients. In many cases, because of molecular testing that has identified a specific mutation, patients can meet other patients with the same genetic mutation. Some end up forming groups (communities) to share their common journey. One example is a group with the identified non-small cell lung cancer (NSCLC) mutation called ROS1. Tori Tomalia, a two-time cancer survivor currently living with stage 4 NSCLC, helped form the group after attended a conference where she made some connections with others with the ROS1 mutation. The group ultimately started a private Facebook page, and began connecting with other patients with the ROS1 mutation. The group became a place for to share treatment journeys, discuss clinical trials, exchange advice on symptom management and pool their knowledge. As the group grew to over 100 people, they realized that they could make an impact and came up with the idea to approach a foundation about doing a custom research study. They realized that they could become their own advocates in a very big way by leveraging their numbers to hopefully move research forward. They contacted The Bonnie J. Addario Lung Cancer Foundation (ALCF) and they agreed to get behind a research initiative.

ROS1 It is a rare mutation that affects only 1-2% of NSCLC diagnoses, but also one that has a currently approved treatment that targets this mutation, crizotinib (Xalkori). Xalkori was initially approved by the U.S. Food and Drug Administration (FDA) to treat patients whose non-small cell lung cancers (NSCLCs) harbor an alteration in a gene called ALK, which occurs in up to 8 percent of patients with the disease. In March, 2016 the FDA expanded the use of Xalkori to include lung cancers with a second abnormality, the ROS-1 gene alteration.  Because ROS1 also occurs in several cancer types including gastric cancer, ovarian cancer, glioblastoma, melanoma etc., ALCF wanted to focus on this under-studied rare molecular subset of cancer and understand what drives oncogenesis and disease progression in these tumors. So in collaboration with this group of cancer patients whose tumors have ROS1 fusions (they call them the ROS1ers), they launched a global effort to study ROS1 fusions across ALL tumor types.

This is a great example of patient empowerment and advocacy, started because a group of patients who met at a medical conference realized together they could make a difference. Using the power of social media, they built a community and took the initiative to approach a foundation to advance research. We’ve come so far with molecular testing – lung cancer patients now realize it’s not just one disease, and there are opportunities to connect with other patients with similar diagnoses. And also the opportunity to find targeted treatments or clinical trials for their specific mutation. I continue to advocate for more research funding because, like with these ROS1ers, we can identify more mutations, build more communities, and discover more targeted treatments.

Tuesday, February 14, 2017

"Get Your Affairs in Order?" Not So Fast

It wasn’t that long ago that a diagnosis of stage 4 Non-Small Cell Lung Cancer (NSCLC) was death sentence. Patients often heard “I’m sorry, there’s nothing more we can do” or “it’s time to get your affairs in order.” Unfortunately, too often that communication still happens today. However, with the advent and increasing availability of molecular testing, we are able to identify biomarkers that can lead to available targeted treatments. My friend Linnea Olson is one shining example of how far we’ve come in lung cancer treatment, and gives me hope for good outcomes if patients get their tumors tested. It’s also why I am such a passionate advocate cancer research and precision medicine.
                                             Linnea (on right) and Dr. Alice Shaw
In 2006, Linnea heard the words ‘there is nothing else we can do.” Never one to turn away from the truth she wanted to know more, she wanted to know how much time remained. The answer was three to five months. And so she began to let go of her life—and to help her family do the same – and started saying her goodbyes. But then at her next oncology appointment something totally unexpected happened. A recent biopsy had been submitted for genetic testing and had come back positive for a newly identified mutation in NSCLC called an ALK translocation. A phase I clinical trial for an experimental agent targeting ALK mutations had begun recruiting at Massachusetts General Hospital (MGH).
In 2008, she became the fourth person in the world with NSCLC to take crizotinib (Xalkori). Seven weeks later, her scans revealed remarkable improvement. She was lucky to be at the right place, at the right time, and with the right oncologist, Dr. Alice Shaw at MGH. Since then she has been a participant in three phase I clinical trials. Of course, she still has lung cancer. But now almost 11 years later she is still inspiring me and other lung cancer research advocates who believe that molecular testing is key to matching specific mutations to targeted treatments.
Since the original discovery of the ALK rearrangement in NSCLC in 2007, small molecule tyrosine kinase inhibitors of ALK have transformed the course of treatment for those patients with ALK-rearranged (ALK-positive) NSCLC. Crizotinib was the first targeted therapy developed for patients with advanced ALK-positive NSCLC and has proven to be superior compared with first line chemotherapy in many global trials. However, patients invariably relapse on crizotinib, often within the first year of treatment, and research has been ongoing, trying to change this.
To address the growing issue of crizotinib resistance, multiple next-generation ALK inhibitors have been developed. The first of these new drugs—ceritinib (Zykadia)—showed significant clinical activity in a global phase I study leading to its approval in the United States, Europe, and elsewhere. Alectinib (Alecensa) now joins ceritinib as another next-generation ALK inhibitor approved in the United States for patients with advanced ALK-positive NSCLC previously treated with crizotinib. These approvals raise several important questions regarding the management of patients with advanced ALK-positive NSCLC. First, in a patient who has relapsed on crizotinib, which next-generation ALK inhibitor should be prescribed? This question does not have a simple answer, since the pattern of relapse can differ from patient to patient. More head-to-head clinical trials comparing next-generation ALK inhibitors need to be performed, but based on the available single-arm studies of alectinib and ceritinib in crizotinib-resistant disease, the systemic efficacy of these drugs may be roughly comparable. Ultimately, the choice of next-generation ALK inhibitor will need to be individualized for each patient.
The second question that needs to be addressed is whether next-generation ALK inhibitors like alectinib should be used in the first-line setting in place of crizotinib. At present, the standard approach—sequential therapy with crizotinib followed by a next-generation ALK inhibitor—is associated with a combined median progression-free survival of 18 to 20 months. Whether first-line use of a next-generation ALK inhibitor can lead to a comparable outcome is not yet known. However, limited data with several of the next-generation ALK inhibitors suggest that this could be the case. The final question concerns resistance to alectinib as new mutations continue to be identified. This will be an ongoing battle and I believe with continued support of cancer research, we will see new treatments matched to the new targets. Considering where we were prior to 2006, there is much hope for patients that are tested and ALK-positive is identified. And like my friend Linnea, patients won’t here “get your affairs in order.”