Abstract PR07: Collateral sensitivity in chemotherapy resistance

The current 5-year survival rate across all cancers is only 68%. The ability of tumors to develop resistance to chemotherapy is a major factor keeping survival rates down. Understanding the evolutionary paths tumors take towards resistance will aid in creating drug regimens designed to avoid resistant tumor states. Research in bacteria suggests that a specific type of drug pair, where resistance to each drug confers sensitivity to the other drug, can slow evolution toward drug resistance. This drug pair relationship, termed collateral sensitivity, has not been systematically investigated in cancer. Here, using a preclinical Eμ-myc; Arf-/- murine model of Burkitt lymphoma we investigate collateral sensitivities in this malignancy. We derived resistant cell lines in vitro by treating the parental cell line with dose escalating concentrations of doxorubicin or cisplatin. We screened a subset of these resistant cell lines against a panel of drugs and found several collateral sensitivities conferred by doxorubicin or cisplatin resistance. We are currently investigating the mechanism of one of these collateral sensitivities. We plan to derive cell lines resistant to a variety of other chemotherapies to learn about collateral sensitivities across many chemotherapeutics. Collateral sensitivity is a promising avenue towards rationally designing combination therapies that reduce the emergence of chemotherapy resistant disease. Citation Format: Simona Dalin, Boyang Zhao, Michael T. Hemann. Collateral sensitivity in chemotherapy resistance [abstract]. In: Proceedings of the AACR Precision Medicine Series: Opportunities and Challenges of Exploiting Synthetic Lethality in Cancer; Jan 4-7, 2017; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2017;16(10 Suppl):Abstract nr PR07.