Title: Heterogeneity and Robustness in Cancer
Speaker: Marsha Rosner (University of Chicago)
Abstract: In the United States, the lifetime probability of developing cancer in one's lifetime is ~40%, and the lifetime probability of dying from cancer is ~20%. The second leading cause of death behind heart disease, cancer is a particularly challenging disease. Unlike heart disease, cancer includes multiple disorders dependent upon the specific tissue type and tumor cell. Cancer is largely driven by genes that push cancer progression, and is enabled by loss of tumor suppressors that normally confer feedback regulation and robustness to cells. For solid tumors, the metastatic process involving colonization of different tissues by cells from the primary tumor is actually the cause of death.
One of the major challenges to treatment of cancer is the evolutionary nature of the process that leads to tumor cell heterogeneity. This process enables cancer cells to adapt to stressful environments and eventual drug resistance. The mechanisms leading to such heterogeneity have largely been attributed to "genetic" processes that mutate DNA and "epigenetic" processes that modify transcription, e.g., the translation of DNA to RNA. However, we have recently published studies that demonstrate a role for very different stochastic, nongenetic processes (that can be either heritable or nonheritable) in establishing phenotypic heterogeneity.
In addition, since single drug treatments have been largely unsuccessful, we have been exploring conceptual frameworks for predicting optimal drug combinations to treat cancer. Cancer drugs ideally kill cancer cells while limiting harm to healthy cells. However, the inherent variance among cells in both cancer and healthy cell populations increases the difficulty of selective drug action. The lack of success with current cancer treatments suggests that we need alternative methodologies that would benefit from interdisciplinary approaches. The goal of my talk is to highlight these aspects of cancer that can potentially be addressed by mathematical analysis.
Seminar URL: http://mbi.osu.edu/programs/mbi-colloquium/