Robert J Norgard, Pratha Budhani, Sarah A O'Brien, Youli Xia, Jessica N Egan, Brianna Flynn, Joshua R Tagore, Joseph Seco, Gregory W Peet, Ania Mikucka, Ruby Wasti, Li-Chuan Chan, Melanie Hinkel, Sandra Martinez-Morilla, Jeanine Pignatelli, Francesca Trapani, Emily Corse, Di Feng, Kaja Kostyrko, Marco H Hofmann, Kang Liu, Abhishek Kashyap
KRAS inhibitors have demonstrated exciting pre-clinical and clinical responses, although resistance occurs rapidly. Here, we investigate the effects of KRAS-targeting therapies on the tumor microenvironment using a library of KRASG12D, p53 mutant, murine PDAC-derived cell lines (KPCY) to leverage immune-oncology combination strategies for long-term tumor efficacy. Our findings show that SOS1 and MEK inhibitors (SOS1i+MEKi) suppressed tumor growth in syngeneic models and increased intra-tumoral CD8+ T cells without durable responses...
May 10, 2024: Cancer Res Commun