Targeting : Crossroads of Signaling and Immune Inhibition.

Mutations of are commonly seen in human cancers, especially in lung, colorectal, and pancreatic adenocarcinoma. Despite huge effort for decades, targeting mutations has been "undruggable" because of the molecular instability of RAS protein inhibition. However, the recent discovery of the G12C inhibitor paved the way to expand therapeutic options for patients with cancer harboring the G12C mutation. At the same time, the successful development of immune checkpoint inhibitors (ICIs) drastically changed the paradigm of cancer treatment and resulted in a better understanding of the tumor immune microenvironment in patients with -mutant cancer. This review describes the following: the clinical characteristics of cancer with mutation; successful development of the G12C inhibitor and its impact on the tumor immune microenvironment; and potential new avenues such as the combination strategy using inhibitor and ICI, with preclinical and clinical rationales for overcoming resistance to inhibition of to improve therapeutic efficacy for patients with cancer harboring mutations.