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
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
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
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
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!
PASSION FOR SCIENCE
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.
FUNDRAISING IS A REALITY
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
MEET JOHNATHAN WHETSTINE
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.
YOU CAN’T FIX WHAT YOU DON’T KNOW
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
HISTORICAL PERSPECTIVE: SEQUENCING
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.
PUTTING YOUR DNA INTO THE GAME
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
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.
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
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
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.”
Monday, January 16, 2017
As I’ve previously written, the most useful biomarkers for predicting the efficacy of targeted therapy in advanced NSCLC are genomic alterations known as "driver mutations." These mutations occur in cancer cells within genes encoding for proteins critical to cell growth and survival. Through the use of molecular testing, the discovery of genetic mutations that drive NSCLC is rapidly improving the outlook for some patients in stage 4 disease. This is significant because almost 40% of lung cancer diagnoses are stage 4 patients. One of the first breakthroughs was the discovery of the EGFR (epidermal growth factor receptor) mutation, which is present in about 10 percent of patients who are diagnosed with lung cancer in the United States (interestingly more common in patients with adenocarcinomas and no prior history of smoking, as well as in women and those of Asian descent).
I remember being at the American Society of Clinical Oncology (ASCO) conference in 2004 and the buzz surrounding a drug called Gefitinib (Iressa). The FDA had approved Iressa in May of 2003 for treatment of Non-Small Cell Lung Cancer (NSCLC) and it was notable that in clinical trials the drug worked spectacularly well in about 10% of lung cancers patients but failed to help the rest. No one could figure out why. Then researchers figured out that most people who responded to Iressa had similar genetic mutations in their tumors. A later study extended the findings in EGFR research to a related drug, Tarceva, which was awaiting approval by the FDA.
The two groups of Harvard researchers, one at Massachusetts General Hospital (MGH) and one at Dana Farber Cancer Institute did a deep dive into the data regarding lung tumors from patients who responded to Iressa and those who did not. Most responders had the EGFR mutations. Non-responders did not. The laboratories began offering a test to detect the mutations and scientists speculated they could become widely available in the near future. MGH had a clinical trial that was testing patients for the mutations as a predictor of their response to Iressa as an initial treatment. Iressa wasn’t usually the first option; it was typically given to lung cancer patients who didn’t respond to chemotherapy. Now that scientists could explain the drug’s effectiveness in some cases, there was hope that they could better predict who would respond to them in the future and that lessons from Iressa and Tarceva could be applied to other cancers. This is when targeted therapy began to become a reality.
Iressa and Tarceva are part of a relatively new class of drugs known as targeted drugs, which are different from traditional chemotherapy drugs because they are designed to specifically hit cancer cells. Unlike chemotherapy drugs which kill healthy and cancerous cells, targeted drugs are supposed to kill only cancer cells. Until the mid-2000’s, treatment options for lung cancer were mostly limited to surgery, chemotherapy and radiation. Now, people diagnosed with lung cancer have newer, more personalized treatment options. The goal of targeted therapy is to accurately target your individual tumor, which hopefully leads to more effective treatments and less side effects.
Thankfully screening has become an increasingly standard part of the diagnostic work-up for NSCLC, and is useful in choosing between standard chemotherapy and targeted therapies. EGFR-targeting drugs — which include Tarceva (erlotinib), Iressa (gefitinib) and Gilotrif (afatinib) — are now used in the first-line treatment for metastatic lung cancer patients. Patients are able to get a treatment that matches the mutation that has been identified through a molecular test of their tumor. While most lung cancer patients with EGFR mutations who respond well to targeted treatments ultimately develop resistance to the drugs after a year or so as the cancer finds other ways to grow, newer drugs are being evaluated to be used as second-line treatments. This is why it’s important to have tumors continuously tested during treatment to detect different mutations that evolve during treatment. For example, Tagrisso (osimertinib) is approved for patients with a specific EGFR mutation called T790M who relapse after being treated with a different EGFR drug. A similar drug called rociletinib (CO-1686) is in late-stage trials in patients with the T790M resistance mutation.
I saw first-hand this process of genetic testing, and the resulting treatment when a good friend of mine was diagnosed with stage 4 lung cancer. He went to the hospital and started chemotherapy treatment. Within 24 hours he was on a ventilator fighting for his life and not responding to the chemo. Test results showed that he had the EGFR exon 19 mutation and his regimen was immediately changed from chemo to Tarceva. He started responding and was off the ventilator breathing on his own within 2 days. We were all blown away with how quickly he responded to the targeted treatment. While unfortunately in his case it was too late to save his life, it did show me how remarkable the response was to a targeted therapy. It also convinced me that every cancer patient deserves to get molecular testing to identify the best course of treatment, which may be a targeted therapy such as Tarceva.
Friday, January 6, 2017
Vice President Joe Biden will be leaving office in 2 weeks. This has me thinking about what role he will play in the cancer community moving forward.
I’ve been optimistic about increased cancer research funding and advances in targeted treatments since President Obama announced his Precision Medicine Initiative (PMI) in early 2015, a research effort focusing on bringing precision medicine to many aspects of healthcare. The mission statement of the PMI is “To enable a new era of medicine through research, technology, and policies that empower patients, researchers and providers to work together toward development of individualized care”. In his budget for fiscal 2016 he included $216 million in funding for the initiative for the NIH, the National Cancer Institute (NCI) and the FDA. I was even more enthusiastic when in his 2016 State of the Union, Obama called on Vice President Biden to lead a new, national “Moonshot” initiative to eliminate cancer as we know it. He launched the National #CancerMoonshot asking for, among other things, $1 billion to provide funding necessary for researchers to accelerate the development of new cancer detection and treatments, with the ultimate goal “to make a decade’s worth of advances in cancer prevention, diagnosis and treatment in 5 years”.
And since the launch of the initiative, Biden, the Cancer Moonshot Task Force and a Blue Ribbon Panel of experts have engaged thousands of cancer patients, caregivers, clinicians, healthcare organizations, advocacy groups, researchers, technologists, and industry leaders in support of the bold mission. In October Biden presented the Blue Ribbon Panel Report, describing 10 transformative recommendations for achieving this ambitious goal. Among the 10 recommendations are support for cancer research including immunotherapy, childhood cancers and a better understanding of tumors – how their cellular and genetic makeup shapes a patient’s response to drugs and how tumors evolve to develop resistance. The report also included announcement of new commitments from both public and private sectors. For example, the NCI, Microsoft and Amazon Web Services announced a collaboration to build a model for maintaining cancer genomic data in the cloud to be available for researchers. And Uber and Lyft offered to expand support of affordable and reliable transportation for cancer patients to address the issue of patients missing appointments. In all, over 70 public-private partnerships were formed, committed to the Cancer Moonshot. And the passage of the 21st Century Cures Act in December of 2016 provided for $1.8 billion reserved for the initiative – very encouraging news.
Fast forward to January, 2017 – what’s next for the #CancerMoonshot program and for cancer research and treatment overall? There is so much uncertainty with a new administration taking over in a couple weeks. I have concerns about the commitment to cancer research, and to affordable care – the cost of cancer treatment. Oncologists are already worried about the cost of treatment. Newly approved cancer drugs cost an average of $10,000 per month, some over $30,000 per month. Patients typically pay 20 to 30 percent out of pocket for drugs, so an average year's worth of new drugs would cost $24,000 to $36,000 in addition to health insurance premiums. This has to be addressed. I understand the pharmaceutical companies invest billions and need to recoup their costs. But there needs to be concerted effort between pharma, insurers, providers and the government to help patients afford these breakthrough treatments. With Republicans now controlling the White House and Congress, it’s unclear what direction the government will go to address any of this. What role will Joe Biden play once he leaves office, and how can we keep the momentum and spirit of collaboration moving forward? Because, as Douglas Lowy, MD, acting director of the NCI said, “the vice president has galvanized the community to move forward so we can greatly increase our ability to prevent, diagnose, and treat cancer”.
I believe one thing is clear. Joe Biden will remain committed to cancer and there is no greater ally to the cancer community. He is said to be forming a nonprofit, currently being called the Biden Cancer Initiative, but the final name could be different. Biden recently said his nonprofit group will focus on many important Moonshot issues including the need to break down the “silos” in cancer research and sharing research data and medical records more widely. He also has talked about boosting participation in clinical trials and the racial disparities that exist in diagnosis and treatment. Biden has been steadfast in his commitment, even in the face of critics who claim beating cancer is far more complicated than putting a man on the moon. He assembled a “Who’s Who” list in cancer for his task force and Blue Ribbon Panel. He brought together all stakeholders, including patients. He has pressed ahead, meeting with researchers and clinicians, repeatedly calling for greater data sharing and collaboration. He lost his son Beau to brain cancer in May 2015. I met him in September 2015. He was very thoughtful and he spoke so eloquently about his losing his son and his determination to lead the way.
We need someone to be the driving force and I have every reason to believe that Joe Biden is the right man to lead this effort to increase collaboration in the cancer community. Whatever direction the new administration may take, I hope Joe Biden will remain the beacon of hope that we can make true precision medicine a reality someday. And let’s hope he also helps energize the philanthropic community to support cancer research.
Friday, December 16, 2016
Lung cancer is the most common cause of cancer mortality globally, responsible for nearly 1 in 5 cancer-related deaths, or an estimated 1.6 million people. In the U.S., lung cancer is by far the leading cause of cancer-related death among both men and women; more deaths are caused by lung cancer every year than by breast, prostate, and colon cancer combined. But after years of modest growth in new treatment options, there is much cause for hope. In 2015, the FDA approved six new drugs for the treatment of lung cancer—a one-year record – including two new immunotherapy drugs, nivolumab (Opdivo®) and pembrolizumab (Keytruda®). These approvals were landmark events for the treatment of lung cancer in 2015.
And the scientific evidence is accumulating that genomic testing and targeted therapies for lung cancer patients, particularly those who have advanced, or metastatic non-small cell lung cancer (NSCLC) make a significant difference in outcomes. The most useful biomarkers for predicting the efficacy of targeted therapy in advanced NSCLC are genomic alterations called "driver mutations”. Genomic tests for driver mutations have become an increasingly standard part of the diagnostic work-up for NSCLC patients, and the testing is useful in choosing whether a patient receives chemotherapy (if there is not a targetable driver mutation) or an FDA-approved targeted therapy up-front. The best characterized of these biomarkers are epidermal growth factor receptor (EGFR) mutations and (anaplastic lymphoma kinase) ALK translocation. Identification of these biomarkers has led to highly targeted treatments that have resulted in major advances in prolonging survival - without the harsh side effects of chemotherapy. Patients with specific genetic mutations may benefit from targeted therapies such as the EGFR blockers erlotinib (Tarceva®), afatinib (Gilotrif®), and gefitinib (Iressa®), to name a few.
Lung cancer treatments are advancing so fast that it’s important to get tested to find out if a patient has an identifiable mutation. Patients with advanced NSCLC, and their caregivers need to have the conversation with their care team about getting tested and understand the abnormality that is causing the cancer. If a therapy exists patients are having good outcomes. If there is not a targetable mutation, patients can find clinical trials that may help prolong life. Not every driver has an effective treatment, but according to the LCMC II study nearly 60% of NSCLC adenocarcinoma patients are likely to have a driver gene that can be targeted with approved drugs or those in a clinical trial. This is amazing progress in lung cancer treatment, and made possible by cancer research. The basic research done 10 years ago is leading to breakthroughs today. It’s why I support the vision of the #CancerMoonshot program’s aim “to make a decade worth of advances in cancer prevention, diagnosis and treatment in five years."
A recent article by Dr. Lecia Sequist (Associate Professor of Medicine, Harvard Medical School) and Dr. Joel Neal (Assistant Professor of Medicine–Oncology, Stanford University/ Stanford Cancer Institute) shares good information about the professional medical organizations that recommend analyzing either the primary NSCLC cancer tumor or a metastatic tumor for EGFR and ALK, regardless of patient characteristics (such as age, race, or smoking history). And The National Comprehensive Cancer Network guidelines for metastatic non-small cell lung cancer strongly recommend testing for alterations in EGFR, ALK, and ROS1 genes, as well a broader genomic panel to look for driver genes that might have clinical trials available. In this shifting landscape in lung cancer treatment, molecular testing may identify a targeted treatment, or help find a clinical trial. Patients need to be their own health care advocates.
Monday, November 28, 2016
I recently attended an event in Boston organized by Elsevier called “The Next Giant Leap” that brought together oncology experts to talk about cancer research and the goals of the White House Cancer Moonshot initiative. The event featured a panel of experts, each approaching cancer research and care from a different perspective, and was centered on the President’s Cancer Panel Report (the Report). The panel discussed improving access to clinical trials, the impact of data sharing on patients and care providers, and how to break down silos and improve collaboration across all sectors.
The theme of the Report was how to improve cancer-related outcomes with connected health. This is an ambitious undertaking: how can we use technology to promote cancer prevention, enhance the experience of cancer care for patients and providers, and accelerate progress in cancer research. As the #CancerResearchEvangelist and a patient advocate, my personal interest in attending was to learn more about how patients can get access to clinical trials and how research can bring more targeted therapy - #PrecisionMedicine - to patients. I’m a strong proponent of the #CancerMoonshot program and its aim "to make a decade worth of advances in cancer prevention, diagnosis and treatment in five years." When I met Vice President Joe Biden last year, I was struck by his sincerity and determination. I applaud Elsevier for bringing together experts to be a part of the national conversation about cancer research and hope that we will see more of these events in the future.
Most will agree that cancer is an area of healthcare that can benefit from improved coordination, communication, and access to information – sharing and integrating data can expedite scientific discovery and more effectively prevent, research and treat cancers. However, according to the Report, “technical, financial, policy, and cultural barriers have precluded optimal development and use of connected health technologies for cancer.” My big questions are how do we break down the silos and facilitate the true collaboration and sharing of data to help advance research. Unprecedented amounts of data about cancer patients are being collected in medical records, in research studies, and by individuals themselves. Traditionally this data remained wherever they were collected and generally were used in limited ways only to serve the specific needs of whoever collected them. All of these silos represent a significant missed opportunity. Connected health technologies have an important role to play by facilitating the linking of data sets and creating tools that enable researchers, clinicians, and patients to use data in meaningful ways. To achieve the development of a national infrastructure to support sharing cancer data, technical and logistical challenges to data integration must be overcome, and the cancer community must foster a culture of collaboration that encourages data sharing and free exchange of ideas. Of course, patient privacy and security of data continue to be issues of concern that must be addressed to facilitate true data sharing and collaboration. I also believe that the government and cancer organizations must balance competition with the goal to make the next big discovery to help patients. The President’s Cancer Panel urges all stakeholders - health IT companies, healthcare providers, researchers, government agencies, and patients - to collaborate in using connected health to improve the experience of cancer care for patients and providers.
Access to Clinical Trials
Clinical trials are essential for advancing knowledge about cancer and for developing better, more targeted treatments for cancer. However, in the U.S. patient participation remains one of the biggest challenges to their success (estimated at less than 5% participation in trials). Although surveys show that patients would be willing to participate in clinical trials if available, many obstacles continue to prevent more broader enrollment – primarily patients not being aware of availability, difficulty determining if they are eligible, and lack of provider referral. The President’s Cancer Panel has identified the tremendous potential of connected health to expand access to clinical trials. A clear role has emerged for online tools – and with social media – to quickly and broadly mobilize communities to participate. In fact many non-profits, advocacy groups and pharmaceutical companies are using social networks like Twitter and Facebook to connect with patients. However, the amount of information and complexity of trial eligibility can be daunting for patients. And matching a patient to specific clinical trial criteria often requires access to the patient’s disease profile (diagnosis, type and stage of tumor, etc.). The Elsevier panel discussion on trials focused on the need for education, patient stories, incentives and the involvement of patient communities (i.e.: the ovarian cancer community of patients connecting to share their experiences).
Next-generation resources that help facilitate the ability for cancer patients to be matched to a clinical trial based on their profile have the ability to transform the way we currently enroll patients. The goal is for these tools to facilitate automated clinical trial matching based on each patient’s personal disease profile. It is my hope that this will also increase the participation beyond the current 5%, and help lead to faster discoveries and ultimately cures. The President’s Cancer Panel Report highlighted one such next-generation online resource for clinical trial matching – The Cure Forward Clinical Trial Exchange. Rather than searching for trials themselves, patients can create their own personal profiles. Based on the molecular testing information and trial preferences provided by the patient, trial recruiters can review this information and contact patients who may be eligible for a given trial. If a patient hasn’t already had molecular testing done, Cure Forward can recommend and direct patients to laboratories that can do the testing. And, as recommended by the Elsevier panel, education and connecting with other similar patients is also an integral part of the process. Cure Forward can connect patients with cancer professionals, called Patient Guides that can help them personally navigate the clinical trial process.
I’m grateful to Elsevier for inviting me to The Next Giant Leap event in Boston, and for the cancer expert panel for their insights. We truly are all in this together.
Tuesday, November 8, 2016
I am building momentum in my role as the Cancer Research Evangelist - with the help of many amazing people. This is not in the religious sense, not preaching about the gospel. No, another meaning for evangelist is “a zealous advocate of something”. Years ago, Guy Kawasaki became the Chief Evangelist at Apple, and popularized the word evangelist in marketing the Macintosh for Apple and the concept of evangelist marketing. In 2006 he wrote about the art of evangelism, and even today it resonates with me because its tenets are perfectly suited for advocating for cancer research. I’ve been writing for months about the need for someone to tenaciously advocate, or “evangelize” about supporting scientists that have to spend 75% of their time fundraising. I was at the CANCERx conference recently and heard Dr. Phil Sharp from MIT reinforce the importance of basic cancer research, and how the NIH needs to lead the way.
With this in mind, I’m looking forward to speaking at Jeff Pulver’s next conference, the #140Conf, “State of NOW” on November 14th in Los Angeles. Jeff is a VoIP pioneer, communications visionary, and connector. I met Jeff last year at the Gratitude and Trust conference he co-hosted in NYC, and am a believer in his vision for real time web communication. Since June 2009, Jeff has brought together people from many different backgrounds, from all over the world to share their stories. He calls it “The State of NOW Experience”. In Jeff’s words, “these conferences provide a platform for people to listen, connect, share, and engage with each other, while collectively exploring the effects of the real-time web on business and in their personal lives.”
I am so grateful for the opportunity to speak at the conference about how I became the Cancer Research Evangelist and why it matters. I’ll talk about how the real time Internet has helped me connect with an amazing community of people who share my passion for supporting cancer research. I call it surrounding myself with good people. People that care.
Friday, September 16, 2016
The Precision Medicine Initiative, launched by President Obama in his 2015 State of the Union speech, aims to extend the concept of precision medicine — the right treatment or prevention plan for the right person at the right time — beyond cancer, where we have seen great progress, to all health conditions. A key part of this effort involves building the Precision Medicine Initiative Cohort Program, a group of at least 1 million Americans who will donate data about themselves, everything from health records to genetic sequences and diet surveys. FDA Chief Dr. Robert Califf thinks that number should be as high as 100 million. Perhaps this may be possible. In a recent survey published in PLOS One more than half of the 2,600 respondents (54 percent) said they would definitely or probably be willing to take part in the program.
The President called for $215 million in fiscal year 2016 to support the Initiative, which includes several components with efforts from across the federal government. Of this total proposed budget, $130 million was allocated to NIH to build a national, participant group, called a cohort, and $70 million was allocated to the National Cancer Institute to lead efforts in cancer genomics. Cancer has shown the most promise in efforts to target treatments to the specific mutations of cancer patients.
One such company leading efforts in helping patients by using precision medicine is Cure Forward, in Cambridge, MA. This is a small team with a vision “to create a platform to connect patients with genomic medicine, bringing the possibilities of precision medicine directly in reach. A way to use the best of technology to help people diagnosed with life-altering disease discover all of their options. We want to make it easy for patients to understand the root cause of their conditions and put the knowledge to work. Get their data, find treatment options, including clinical trials.” I recently met with the Founder, Martin Naley, and my friend Alicia Staley, Patient Advocate to catch up on their progress. It’s an exciting vision to teach patients about molecular diagnostic testing, precision medicine, connect with other patients, and help them get into clinical trials.
I’m optimist about the direction we are going with precision medicine. While some have been critical of Vice President Joe Biden’s “Moonshot”, his Summit showed that there are a lot of very smart people involved and getting behind the effort. Yes it is complicated, but once again shows the need for collaboration in the fight against cancer. As I have written about many times, “we are all in this together”.
Wednesday, August 24, 2016
Meet Johnathan Whetstine, PhD.
Cancer cells that stop responding to treatment (drug resistance) are a common cause of cancer deaths. Researchers are trying to understand how to treat resistance, and/or prevent it in the quest for the next generation of cancer therapies that can save lives. One such researcher, Johnathan Whetstine, PhD and his team in the Whetstine Laboratory at the Mass General Center for Cancer Research is studying how cancer cells become drug-resistant. They recently uncovered a protein that generates specific DNA fragments containing genes that cause cancer cells to become resistant to chemotherapy. This allows replicating cancer cells to grow and defend themselves against previously effective treatments. We all know how devious cancer cells are in trying to outsmart treatments.
The Whetstine Laboratory’s discovery was the first of its kind, and provides a new way to understand how cancer cells change their DNA content and potentially acquire the ability to become treatment resistant. In fact, their discovery identified a new protein to evaluate in tumors and directly relates to cancer cell response to therapy. Most recently, Dr. Whetstine’s group used a drug to target the protein and was able to block the extra DNA pieces associated with drug resistance. These findings illustrate the importance of evaluating this protein in tumors and demonstrate that this process does not occur randomly but can be directed and targeted by proteins within the cell. Dr. Whetstine’s group is currently uncovering additional genes and conditions that can generate extra DNA pieces involved in cancer cell drug resistance. This work holds promise for the development of new strategies to block resistances to chemotherapies and targeted therapies with broad and profound implications for many different types of cancer.
Tumor cells contain extra copies of DNA that ultimately contribute to their lack of response to chemotherapeutics and aggressive behavior. The Whetstine Laboratory is working to uncover the genes and proteins that promote copy gains of DNA regions and stimulate resistance to help identify novel drug targets associated with aggressive drug resistant cancer and provide novel biomarkers to evaluate in patients during the course of therapy so that resistance may be predicted earlier. The Whetstine Laboratory has now unlocked a way to better understand copy gains related to tumorigenesis and have firmly established that these events are regulated.
The Whetstine’s Laboratory is another of the research programs that needs philanthropic support – in this case to investigate how treatment resistance occurs, how we can think about blocking drug resistance and how we can help identify patients who are most vulnerable to emerging drug resistance. Their studies are currently aimed at addressing this question in lung cancer, ovarian cancer, myeloma, breast cancer and neuroblastoma.
One of the Disruptive Dozen
The culture of innovation at Massachusetts General Hospital and Brigham and Women’s Hospital —throughout all of Partners HealthCare and collaborating institutions such as Dana-Farber Cancer Institute—naturally fosters a good deal of discussion about new “disruptive” technologies and which ones will have the biggest impact in bringing novel complex health care products and services to greater levels of affordability and accessibility. The mission of Partners clinicians and researchers to provide the best care for patients drives a continuous dialogue on what state-of-the-art medical technologies are just over the horizon. The Disruptive Dozen was created to identify and rank the most disruptive technologies that Partners leading faculty feel will break through over the next decade in cancer care.
Johnathan Whetstine was recognized for his work at the Partners World Medical Innovation Forum in April as one of the most promising technologies (number 5) that will have significant impact on cancer care in the next 10 years. He and his wife are also our friends, and fellow MGH one hundred honorees. #gratitude