Role of epigenetics in cancer drug resistance
Wednesday, June 6, 2018 - 11:00am - 11:30am
It has been observed experimentally that epigenetic phenomena can induce temporary or reversible drug-resistant phenotypes in cancer cell populations. For example, changes in methylation status of DNA repair genes may impact the responsiveness of cells to chemotherapies. Although these phenomena may be transient, they can have lasting impact on the genetic evolution of a tumor. Short-term epigenetic adaptations may serve as temporary lifelines for a population until more permanent genetic resistance mechanisms can be established. In this talk I will propose a few mathematical models (from the population dynamics viewpoint) of the co-evolutionary process between the genome and epigenome. Using these models, we can query the role of epigenetics in the genetic progression of tumors, e.g. does epigenetic phenomena speed up or slow down genetic tumor evolution? To what extent does epigenetic phenomena impact response to therapy? Can temporary epigenetic phenomena supplant the role of permanent genetic resistance mechanisms? An application to TMZ resistance in glioblastoma via promoter methylation of the MGMT gene will be discussed.