Advances in drug development have produced many new effective cancer therapies but evolution of resistance remains a fundamental barrier to cure or prolonged control. Recent investigations of the Darwinian dynamics that govern proliferation of resistant cancer populations suggests evolution-based strategies may improve cancer treatment outcomes.

The molecular mechanisms leading to disease progression and refractory disease in Multiple Myeloma (MM) remain poorly understood. Here we demonstrate preliminary data from a new cohort of MM patients, suggesting that multiple independent combinations of genetic and epigenetic events alter genome-wide transcriptional reprogramming, facilitating disease progression and emergence of therapy resistance.

Tumor heterogeneity creates obstacles for treating cancer, such as a difference in susceptibilities to treatment, natural selection for drug resistance, and the possibility for interactions among cells to alter treatment response. With the use of an ER+ breast cancer in vitro system, we are able to investigate ecological interactions between cells sensitive and resistant to selective drug pressure in heterogenous cancer populations to probe for differences in growth, resistance, and cooperative communication between cell types. In doing so, we can better understand the consequences of these interactions and how they drive the evolution of therapy resistance in order to identify targets for long-term treatment strategies and combat refractory tumors.