A Conversation about Cancer: Six Questions that Keep Cancer Experts Up at Night

What keeps you up at night? This was the question posed by Kimmel Cancer Center director William Nelson, M.D., Ph.D., to six cancer experts who participated in a Cancer Conversations forum on Nov. 3, 2015. In parts one and two of this series, they predicted the future of cancer medicine and discussed how they collaborate with other scientists. The panelists were:

• Kimmel Professor and Director of Radiation Oncology and Molecular Radiation Sciences Theodore DeWeese,
• Kimmel Scholar and GI cancer pathologist Laura Wood,
• Kimmel Scholar and cancer biology cell division scientist Andrew Holland,
• Martin D. Abeloff Scholar in Cancer Prevention and Control and Deputy Chair in the Department of Epidemiology at the Johns Hopkins Bloomberg School of Public Health Elizabeth Platz,
• Co-Director of Cancer Immunology Charles Drake, and
• gene sequencing expert Vasan Yegnasubramanian.

Questions That Keep Cancer Experts Up At Night

Yegnasubramanian:  How can we fill unmet clinical needs? I think about better biomarkers to test for and distinguish aggressive cancers from non-aggressive cancers so that we intervene earlier against aggressive cancers. Despite out best efforts, cancers alter their physiology and evade therapies. We need increased options for patients with advanced cancers and to devise combination therapies to treat initial disease and avoid resistance.

DeWeese: How can we decrease overtreatment and the harm it causes to patients? My goal is the development of a radiation signature for each patient that tells us which patients will require more treatment and what patients could be successfully treated with lower doses.

Chuck Drake: We are seeing remarkable responses with immune therapies, particularly with an immune target called PD-1. I saw two patients from our very first anti-PD1 trial who are still alive. Unfortunately, there are many patients who are not. I want to understand why those patients are still alive and others are not. What was different about their cancers and their immune systems?

Platz:  I think about measuring exposure and classifying people with respect to their exposures so we really can figure out what is causing cancer on a population level. The things we know about—smoking, obesity and physical activity—only explain about 50 percent of cancers in the population. What about the other 50 percent? In addition, there is a need to figure out ways to translate what we’ve learned about prevention into behavior changes so that we reduce the risk of cancer on a population scale and create healthier survivorship.

Holland:  I think about the variation in singles cells of the same type. We look at cells and they seem identical, and at the genetic level, they may be.  But, at the expression level they vary dramatically, but yet they behave very much the same. How does this relate to treatment resistance?

Wood:  I want to find biomarkers that distinguish common low-risk precancerous lesions from uncommon high-risk precancers so that we can identify and treat high-risk precancers and not overtreat those at low risk. There are still many gene variants that we don’t understand. We need to figure out which ones matter—how genes interact and what mutations are important. I envision new model systems to test for the relevance of mutations to cancer versus alterations that are just along for the ride.

Watch the forum: