This month we talk to Raymond Meyn, Ph.D. and Heath Skinner, M.D., Ph.D., whose laboratories are jointly tackling questions of radiation resistance and radiation sensitivity in head and neck tumors. Their work has been published in Clinical Cancer Research, Oncotarget, Oncogene, among others and they continue to submit and receive grants together. As collaborators on three active research grants, we asked them a few questions on their joint work in radiation science.
How did you get interested in radiation science?
Dr. Meyn: As a student, I liked sciences, especially physics and biology. I had a hard time deciding which to study. Once I took an introductory course on Radiation Biophysics, I realized that this subject combined both of my interests.
Dr. Skinner: In my fourth year of medical school I was first introduced to both radiation oncology as a specialty as well as radiation science as a discipline. As I learned more about the clinical use of radiation to treat malignancy I also became interested in examining the biology of why what we did sometimes worked and sometimes did not. This simplistic question has proven to be nearly intractable, yet still intrigues me
How did you start working together?
Dr. Skinner: Dr. Meyn and I began working together where I was a resident at MDACC, pursuing studies in the laboratory of Dr. Jeffrey Myers. Dr. Meyn was kind enough to share the wealth of experience gained through decades of studying radiobiology. We soon realized that we were interested in same questions which led us to pursue joint projects. This has grown into a strong collaboration since I joined the faculty in 2012.
Dr. Meyn: As I recall, Heath approached me and asked for help with a project concerning p53 mutations and assays for radiation sensitivity of cell lines with such mutations. At the same time, I was taking over a project started by Dr. Kian Ang on the impact of HPV on radiation response in head and neck tumors. As Heath was working on the Head and Neck Service and was very interested in the HPV story, we kept discussing the project and related questions. These conversations evolved into an active collaboration and we just submitted our first R01 together.
What are the questions being pursued in your group?
Dr. Meyn: For the past several years, my group has been focused on assessing molecular targeted agents as radiation sensitizers. This has been very successful with several such agents going on to clinical trials in combination with radiotherapy. For example, we demonstrated that MK-1775, a wee kinase inhibitor, acts as a radiation sensitizer. It is very exciting to see that there are 4 ongoing clinical trials combining MK-1775 with radiation (clinicaltrials.org).
Dr. Skinner: Primarily we are utilizing a variety of different means to investigate novel, targetable biomarkers of resistance to radiotherapy.
What challenges do you see ahead for our field?
Dr. Skinner: The current funding climate is a big factor. At present, the funding for all research, but especially for radiation research, is stagnant at best.
Dr. Meyn: I’ll second Heath on funding being a major challenge. But aside from funding, the major advances in radiation science in the last 40-50 years have come from physics: the development of very sophisticated, imaging-based treatment planning systems, IMRT, and proton therapy. They have all been exciting and have improved patient outcomes. But the biologically-based innovations in treatment of head and neck cancer has been the addition of cisplatinum to radiation in the 1970s and, more recently, cetuximab. This is despite a tremendous research effort from radiation biologists who have identified a number of novel radiation sensitizers based on molecularly targeted agents. Some of these new sensitizers are worth exploring in clinical trials.
What excites you the most about the future of radiation science?
Dr. Meyn: The same thing that worries me – there is a large body of research on various biologics leading to improvements in the clinical use of radiation for cancer treatments. Immunotherapy has been an exciting development – every service should explore immunotherapy with radiation. The advent of various repair inhibitors is also exciting.
Dr. Skinner: Like Dr. Meyn, I am excited about the interplay between immune response and radiation treatment – an interplay we are just beginning to understand. Another key development that is being translated into the realm of clinically focused radiation research is molecular biomarker analysis. These developments, if properly utilized, could lead to substantial benefits to our patients.