Abstract B28: Overcoming drug resistance to Trk inhibition by rational combination of entrectinib and trametinib: from bench to bedside

In conclusion, we have identified a mitigation strategy, utilizing an approved agent combined with a well-characterized clinical stage agent, to overcome acquired Trk-inhibitor resistance, presumably by overcoming solvent front mutation-driven MAPK activation. The successful translation of a preclinical observation made at the bench to clinical practice at the bedside has greatly extended the duration of tumor regression and provided continued care to a Trk-fusion positive patient even after the emergence of resistance. This clinical observation will be further explored in a dedicated Phase 1/1b combination study.Citation Format: Ge Wei, Edna Chow Maneval, Vanessa Esquibel, Michael F. Berger, Sofia Haque, Roopal Patel, Colin Walsh, Zachary Hornby, Pratik Multani, Gary Li. Overcoming drug resistance to Trk inhibition by rational combination of entrectinib and trametinib: from bench to bedside [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 B28.
Source: Molecular Cancer Therapeutics - Category: Cancer & Oncology Authors: Tags: Other Topics: Oral Presentations - Proffered Abstracts Source Type: research