Abstract IA10: Improving existing cancer therapy by targeting the tumor microenvironment

Abstract

Abstract Many human cancers fail to respond to chemotherapy, and cancers that initially respond frequently acquire drug resistance and relapse. This process of tumor relapse is particularly confounding, as patients can be in remission for years following treatment prior to the reemergence of a cancer. Additionally, tumors that relapse have generally acquired resistance to the initial treatment. While conventional anti-cancer therapies have been in clinical use for decades, little is known about the mechanisms by which a tumor cell can survive treatment and persist in a patient for extended period of time. In fact, a major cause of cancer deaths is the inability to eradicate small sets of surviving tumor cells, termed “minimal residual disease” or “MRD”. Work from our laboratory has found that chemotherapy paradoxically elicits a pro-survival response in certain anatomical cites. Specifically, normal cells proximal to tumor cells secrete factors that counter the effects of the chemotherapy. This survival response likely serves to protect normal progenitor and stem cells to allow for tissue regeneration following damage, but it is coopted by tumor cells that find themselves in these specialized sites. Thus, effective cancer therapy may not only involve targeting cancer cells but also may require inhibiting survival signals emanating from surrounding cells. We have developed multiple models of MRD that have not only identified mechanisms of tumor cell persistence, but also strategies to sensitize chemorefractory tumors to front-line chemotherapy. Citation Format: Christian Pallasch, Luke Gilbert, Michael Hemann. Improving existing cancer therapy by targeting the tumor microenvironment. [abstract]. In: Proceedings of the AACR Special Conference: The Translational Impact of Model Organisms in Cancer; Nov 5-8, 2013; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2014;12(11 Suppl):Abstract nr IA10.