, describe why KRAS-targeted monotherapy likely is not enough to completely eliminate tumors, suggesting that engaging the immune system is needed to prevent relapse. The comprehensive models generated for this investigation more accurately reflect the tumor microenvironment found in patients with metastatic disease, allowing for rigorous testing that provided unique insights into how oncogenic KRAS allows tumors to escape cancer cell death.
"By extensively testing the functional role of KRAS, we gained important insights into how better to prime the tumor microenvironment in advancedto improve treatment responses," Kalluri said."These results are a testament to the value of team science and to the incredible research environment at MD Anderson, which enables the accelerated and seamless translation from genetic models to clinical application.
This demonstrated that oncogenic KRAS epigenetically blocks expression of the Fas protein, silencing the pathway and allowing cancer cells to avoid an anti-tumor immune response. Suppressing KRAS led to complete tumor regression and significantly improved survival in these models, suggesting the potential for KRAS inhibition to improve immunotherapy responses and prevent relapse.