Abstract A7: Drug resistant murine tumor models facilitate development of next generation anticancer therapeutics

Abstract

Abstract Despite the success in the development of new anti-cancer drugs, all cancer therapeutics, either conventional cytotoxic chemo- or targeted therapeutics, are limited by the drug resistance. Resistance may be divided into two broad categories: intrinsic/de novo or acquired, involving various mechanisms. Certain patients are de novo resistant to a specific therapy, while others initially responded, but eventually recurred with resistant tumors that no longer respond to the original therapy. Even with the newly developed immunotherapies that promise to have long lasting tumor inhibitory effect in patients, a large percentage of patients still do not respond to the therapy. To overcome the resistance to the existing drugs, effective new strategies, e.g. next-generation selective inhibitors, rational drug combinations, and new drug delivery or formulation designs, are developed and under active preclinical and clinical investigations. To enable a more informative selection of resistant models for in vivo preclinical drug evaluation, here we set out to identify a series of animal models, which are intrinsically resistant to either chemotherapy, targeted therapy, or immunotherapy, from more than 200 CrownBio validated cell line xenograft and syngeneic tumor models. On another hand, we also validated a panel of acquired drug resistant models, covering the resistance to Doxorubicin, Imatinib, Elotinib, Quizartinib, Crizotinib or Androgen ablation (castration), etc. The possible mechanisms of some resistance were discussed. In conclusion, these resistant models provide a valuable platform for the development of new strategies to overcome the drug resistance. Citation Format: Ying Jin, Juan Zhang, Dandan Zhu, Yanmei Sun, Guanping Mao, Minxia Wang, Qian Shi. Drug resistant murine tumor models facilitate development of next generation anticancer therapeutics. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr A7.