Our first bioRxiv pre-print! KRASG12C inhibitors are now in clinical trials for oncogenic KRASG12C-driven tumors including Pancreatic Cancer and Lung Cancer and patients are showing responses. As one concern based on experience with other targeted therapies is development of resistance, we modeled development of adaptation/resistance to KRASG12C pharmacologic inhibition and used mass-spectrometry-based quantitative temporal proteomics to understand how adaptation to these inhibitors could develop over time. We next used this proteomic information to design and test drug combinations to enhance response to KRASG12C monotherapy. Combinations with CDK4/6i and HSP90i showed promise but would require further extensive pre-clinical testing to validate. All of our quantitative temporal proteomic data is available via an interactive website:
We’re excited to get feedback via the pre-print process! Great work from co-first authors Naiara Santana-Codina and Amrita Singh Chandhoke! Thanks to collaborators, Drs. Nathanael Gray, Wojciech Fendler and Andy Aguirre.
Our first bioRxiv pre-print: Defining and targeting adaptations to oncogenic KRASG12C inhibition using quantitative temporal proteomics