Blakely and Smith Named 2018 Damon Runyon Clinical Investigators

Blakely: I was thrilled! It is a tremendous honor. The Damon Runyon Cancer Research Foundation has an outstanding reputation for supporting future leaders in cancer research. I am humbled to be chosen for this award.

Smith: I was incredibly honored to receive the Damon Runyon Clinical Investigator Award because it is an award specifically intended to support physician-scientists in performing “bench-to-bedside research.” As the focus of the award is on disease-oriented research investigating human subjects and human disease samples, I felt that this award was designed to nurture my perspective as an MD-trained physician scientist. Receiving this award provided particular validation that I can have an important and unique impact as a scientist because of and not in spite of my work as a clinician.

Blakely: The focus of my research is on understanding why lung cancers with a specific genetic mutation in the EGFR gene do not completely respond to EGFR-targeted therapy. My goal is to understand the co-factors that contribute to EGFR inhibitor resistance and to identify new therapeutic approaches that may be able to overcome these cancer-driving alterations, be they additional genetic events or signals from tumor supporting immune cells. Ultimately, my hope is that this leads to new therapies for lung cancer patients that extends their lives.

Smith: The focus of my research is on a molecular subtype of acute myeloid leukemia (AML) that is characterized by mutations in the receptor tyrosine kinase FLT3. FLT3 mutations are the most common genetic lesions in AML and are associated with poor clinical outcomes. I want to to better understand the structural and functional regulation of FLT3 kinase and how mutations impact function. We also want to understand the effector pathways most critical to the oncogenic function of FLT3 and how these are influenced by targeted therapy. We have observed that patients with FLT3 mutations who are treated on FLT3 targeted therapy almost invariably relapse due to reactivation of FLT3 or its downstream effector RAS. We seek to leverage these observations in patients into enhanced understanding of FLT3 molecular function, and we hope that this work will result in novel targeted therapeutic strategies that can improve outcomes for patients with this common and aggressive subtype of AML.

Blakely: I have always been driven to explore the unknown through science. One of the biggest unknowns in medicine is how to overcome the devastating effects of metastatic cancer. Working as a physician-scientist and oncologist, I hope that I will be able to make new discoveries that improve our understanding of the disease and also lead to new cancer treatments.

Smith: First and foremost, I decided to pursue medicine to take care of patients. I enjoy the relationship that I have with my patients and the privileged insight I have into their lives. I decided on a career in academic medicine because I wanted to contribute new knowledge to improve patient care. In the lab and in clinical research, we can push the envelope to explore new ways to tackle hard problems in medicine that no one has solved yet. In academia, we have the unique freedom to decide which problems are most important to us and how we want to go about solving them. My decision to pursue oncology and specifically, a focus on acute leukemia, stemmed from my experiences caring for leukemia patients, who are some of the sickest of all oncology patients. I felt that this was a patient population that really needed everything I could contribute both as a clinician and a scientist. Additionally, at the time I was doing my residency training, targeted therapy had just come into use in oncology. At the same time, the molecular understanding of leukemia was leaping forward with the development of advanced genomic technologies. It felt like a very exciting time to become an oncologist.

Blakely: I am primarily motivated by my patients, who are in desperate need for new therapies, but also by my own curiosity and drive to make new discoveries that push the boundaries of our knowledge.

Smith: It really comes down to a belief that this work can really make a difference to patients, and that as a clinician and a scientist I am especially positioned to answer questions that really matter to patients. I have chosen to focus on a subtype of leukemia that is very difficult to treat, and even more so, have an emphasis on relapsed and refractory disease-the worst of the worst. To solve hard problems, you must persevere or you will never solve them. Perseverance is certainly a job requirement, but so is hope. As a physician, when one of my patients has a bad outcome, I can hold onto the hope that the work we are doing in the lab will make a difference for the next patient. That is the ultimate motivation.

Blakely: Mentors have been tremendously valuable and influential to me. This started with my graduate school mentor, Lewis Chodosh, at the University of Pennsylvania. Lewis taught me how to think about every problem from a scientific viewpoint. Training in his lab also taught me the value of perseverance and following a project to completion. My fellowship- and current mentor, Trever Bivona, has also significantly impacted my career in a positive way. He has taught me to always ask the tough questions, and that anything worth doing will not be easy and to never give up on something just because it is hard. That is how the most important discoveries are made.

Smith: It is not an exaggeration to say that without my mentors, I would not have a career. Mentorship has been critical to me, as it is to every scientist. My mentors, particularly my K08 mentors, Neil Shah and Kevin Shannon, believed in me before I believed in myself. They provided, in different ways, opportunity and support, material, intellectual and emotional, that enabled and facilitated my development as a scientist. Any success I have had or will have in my career, has been built upon the foundation that my mentors have provided to me. I can’t thank them enough.

Blakely: This is a very challenging field, but also highly rewarding. Don’t expect anything to be easy, but if you can persevere through the difficult times, the good times can be quite worthwhile and exciting.

Smith: Find a problem that you are passionate about and find mentors who believe in you. Science is hard, but it provides unique opportunities for creativity, for discovery and for impact that are hard to replicate elsewhere. I feel lucky to be a physician-scientist.