Welcome to the latest round of Lab Chat, in which our resident Post-Doctoral Research Associate attempts to demystify the often complex and mysterious field of biomedical research. Today, our intrepid writer takes on the roadblocks to diagnosing and treating cancer -- and how improvements in medical technology are offering avenues to better results.
More than one million Americans are diagnosed with cancer annually. But cancer is not a single disease with a single treatment, but rather thousands of diseases that differ from patient to patient and even organ to organ within a single patient. What’s more, the disease evolves over the course of a patient’s lifetime, so at a molecular level a cancer might change week to week. And while medical research continues to find effective therapies to treat many forms of cancer, the notion of a “cure” for cancer is not very realistic because a treatment regimen that eradicates disease from one patient may be completely ineffective for another.
Ours bodies are composed of trillions of healthy cells, each serving a defined purpose and undergoing rigorous checkpoints to ensure their health and survival. In normal tissues, these cells grow and divide to create new cells, while the old, damaged cells die off to make room for healthy ones. However, we are increasingly able to identify the influence of internal and external factors that can compromise the integrity of the healthy cell lifecycle. These factors include age, lifestyle, genetics, DNA damage and exposure to carcinogens. The cause of a particular cancer might be the result of one or many of these factors.
Let’s say that Patient A developed melanoma as a result of overexposure to UV light; the one-two punch of long days on the boardwalk followed by long stints in the tanning bed led to skin damage that has become cancerous. Patient B, however, developed melanoma as a result of two inherited gene mutations from his mother, CDKN2A and CDK4
, which affect the ability of a cell to halt uncontrolled growth. Even though these two cancers might be categorized as the same disease, they will have completely different genetic signatures and likely respond uniquely to the standard of care for melanoma.
Thus, it becomes important to identify genetic patterns that exist between groups of patients to determine how best to treat a class of diseases. For example, certain DNA sequences from Patient A might suggest that he should receive a treatment regimen consisting of the chemotherapy drugs Temozolomide and Cisplatin, while Patient B’s genetic pattern would suggest resistance to these drugs, so he would have to receive an entirely different treatment regimen such as the drug Paclitaxel followed by interferon therapy.
The good news is that this form of “personalized medicine” is becoming more common thanks to technological advances that allow doctors to better analyze and understand the information our DNA is telling us. Additionally, this approach can help minimize the off-target side effects of chemotherapy by analyzing whether particular genetic sequences or mutations would lead to toxicity in a certain patient population.
Here to further explain this concept and offer real-life examples is Dr. Mohamed Abazeed, MD, PhD., one of Cleveland’s brightest new scientific minds. Dr. Abazeed was recruited to the Cleveland Clinic
in late 2013 after a residency in Radiation Oncology at Boston’s Brigham and Women’s Hospital followed by a postdoctoral appointment at the Broad Institute of MIT and Harvard. Dr. Abazeed’s general research interest is in matching genetic mutations with resistance patterns to allow for patient-specific targeted treatment. After an exceptional training and publication history, Dr. Abazeed is destined to push the local medical field towards achieving its goal of better understanding and treating cancer.
Where did you grow up and how did you become interested in medicine?
By the age of eight I was a resident of four continents: Africa, Asia (Middle East), Europe and North America. That early experience clearly shaped my view of the world and my trajectory in it. My family settled in Michigan and I grew up like any other Midwesterner. Hardened by the long winters, I took solace in sports and looked forward to summer barbecues, baseball and trips to Cedar Point. Before I started my undergraduate studies, my father pulled me aside and firmly told me, “I don’t want you to go to college to be a doctor, lawyer, engineer, musician or even dancer. Just get an education!” So I did. I fell in love with science and medicine not through an arrangement, but by natural affinity. I was fascinated by scientific legends and their stories: Kornberg, Watson and Crick, Pauling, Burg… And I really
love difficult problems.
Can you tell us a little bit about your work and your goals in cancer research?
Cancer is heterogenous, as you so nicely describe in your introduction, and it is quite adept at resisting a vast majority of our therapies. Our lab’s effort is to catalogue and target genetic alterations that confer resistance to therapies. Fundamentally, we hunt for mutations and other alterations that represent the Achilles’ heal of cancers when used in combination with current modalities. We use computation, high-throughput technology and a comprehensive target validation scheme in an attempt to bring new molecular diagnostics into the clinic.
How are improvements in medical technology helping to diagnose and treat cancer? Can you give us an example from your own lab?
There have been substantial technical advances in cancer diagnostics and therapeutics in the last two decades. The use of functional imaging is a great example of the former and targeted therapy is a great example of the latter. In our lab, we’ve catalogued determinants of resistance to non-small cell lung cancer (NSCLC). Notably, we identified a pathway that makes about 30 percent of patients with NSCLC resistant to the main therapies used against it: chemotherapy and radiation. In collaboration with commercial partners, we are working to develop a molecular diagnostic that can help identify lung cancer patients resistant to therapy and use a drug to target this pathway to overcome resistance.
Tell us a little bit about the transition in life from Boston to Cleveland.
Boston was fantastic place to train and live. The best Italian food outside of Italy, ferries to the Cape, Red Sox games, and the list goes on. Cleveland’s beauty is in its character and people. I’m really a Midwesterner at heart. I enjoy it when people ask me how my weekend was and seem genuinely interested in the answer. Or when my patients hand me a hand-written note of gratitude that usually comes with a bottle of maple syrup or a cranberry pie.
Red Sox or Indians?
Neither. Go Tigers!
For more information on Dr. Abazeed you can visit his Cleveland Clinic webpage here. Amar Desai is a Post-Doctoral Research Associate in the Department of Hematology/Oncology at Case Western Reserve University. When he’s not getting bronzed in the tanning bed you can contact him here.