Abstract 2073: Profiling and comparison of breast cancer standard of care agents using the OncoPanel™ cell-based profiling service

Oncology drugs with clinical utility for the treatment of breast cancer span a wide range of different mechanisms and cancer type profiles. Anti-cancer therapies have come a long way from the early use of broad spectrum, cytotoxic agents, with mechanisms that often result in harsh side-effects. The advent of more focused, targeted therapies has afforded the potential for not only fewer side effects, but also the ability to provide more efficacious combination therapies with a greater potential for clinical efficacy. Recent advances have seen the approval of agents targeting CDK4/6, Her2, and PARP over the last ten years. Profiling of candidate molecules for eventual use in a therapeutic setting is an essential component of the drug discovery and development process. Understanding not only the biological potency of a candidate drug, but also the breadth of indications for which it may provide clinical benefit, is paramount in the advancement of molecules for clinical testing. Furthermore, understanding something of both the molecular mechanism and the possibility for combination synergy is an essential part of being able to visualize the full clinical potential of a drug. In the current era of personalized medicine, and understanding of the effect of genomic composition of a particular patient’s tumor on clinical outcome, the ability to evaluate a vast array of genomic signatures is important in being able to successfully direct therapeutic application. Eurofins’ OncoPanel cell-based profiling service provides a convenient way for drug hunters to evaluate not only the potential indication spectrum of a candidate molecule by high-content imaging analysis, but also to identify potentially predictive genomic biomarkers for both sensitivity and resistance to these agents. We have evaluated a range of different approved breast cancer therapeutic agents, using the OncoPanel platform, for their effect on the growth of human tumor cell lines in vitro. These agents span a range of different mechanisms and therapeutic modalities, from broad spectrum cytotoxics to more targeted small molecule and antibody drugs. In this poster, we compare and contrast the different utilities of these drugs, both from the perspective of which tumor types and sub-types are sensitive to these agents, but also with regard to which genomic biomarkers are associated with sensitivity toward them. In doing so, we show how these biomarkers can be useful in not only identifying potentially responsive patient subsets, but also potential combination studies that could be used to improve therapeutic outcome. Citation Format: Alastair J. King, Lee R. Cavedine, Alyssa M. Croff, Kristin C. Dempsey, Brogan A. Epkins, Steven M. Garner, Tracy Lu, Victoria V. McBain, Joseph W. Murphy, Vanessa L. Norman, Natiya E. Robinson, Kayla A. Stehle, Charles R. Wageman, Jesse J. Parry. Profiling and comparison of breast cancer standard of care agents using the OncoPanel™ cell-based profiling service [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2073.