Wednesday, August 24, 2016

Addressing the Problem of Drug-Resistant Cancer

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