@article{055e3df042c748ef8ed438d7ee70de65,
title = "Targeting KRAS: Crossroads of Signaling and Immune Inhibition",
abstract = "Mutations of RAS are commonly seen in human cancers, especially in lung, colorectal, and pancreatic adenocarcinoma. Despite huge effort for decades, targeting RAS mutations has been {\textquoteleft}{\textquoteleft}undruggable{\textquoteright}{\textquoteright} because of the molecular instability of RAS protein inhibition. However, the recent discovery of the KRAS G12C inhibitor paved the way to expand therapeutic options for patients with cancer harboring the KRAS 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 KRAS-mutant cancer. This review describes the following: the clinical characteristics of cancer with KRAS mutation; successful development of the KRAS G12C inhibitor and its impact on the tumor immune microenvironment; and potential new avenues such as the combination strategy using KRAS inhibitor and ICI, with preclinical and clinical rationales for overcoming resistance to inhibition of KRAS to improve therapeutic efficacy for patients with cancer harboring KRAS mutations.",
keywords = "KRAS G12C inhibitor, KRAS mutation, immune checkpoint inhibitor, tumor immune microenvironment",
author = "Shumei Kato and Yu Fujiwara and Hong, {David S.}",
note = "Funding Information: Conflict of Interest: Shumei Kato serves as a consultant for Medpace, Foundation Medicine, NeoGenomics, and CureMatch; serves on the advisory board for Pfizer; receives speaker{\textquoteright}s fees from Roche and Bayer and research funding from ACT Genomics, Sysmex, Konica Minolta, OmniSeq, and Personalis. David S. Hong receives research or grant funding from AbbVie, Adaptimmune, Adlai Nortye, Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Daiichi-Sankyo, Eisai, Eli Lilly, EMD Serono, Erasca, Fate Therapeutics, Genentech, Genmab, GlaxoSmithKline, Ignyta, Infinity, Kite, Kyowa, LOXO, Merck, MedImmune, Millenium, Mirati, miRNA, Molecular Templates, Mologen, Navier, NCI-CTEP, Novartis, Numab, Pfizer, Seattle Genetics, Takeda, Turning Point Therapeutics, Verstatem, and VM Oncology; travel support from AACR, Amgen, ASCO, AstraZeneca, Bayer, Celgene, Eli Lilly, Genentech, Genmab, GlaxoSmithKline, Janssen, LOXO, miRNA, Pfizer, Philips, SITC, and Takeda Consulting; serves in a speaker or advisory role for Alpha Insights, Acuta, Amgen, Axiom, Adaptimmune, Baxter, Bayer, Boxer Capital, COG, Ecor1, Genentech, GLG, Group H, Guidepoint, HCW Precision, Infinity, Janssen, Merrimack, Medscape, Numab, Pfizer, Prime Oncology, Seattle Genetics, ST Cube, Takeda, Tavistock, Trieza Therapeutics, and WebMD; and has other ownership interests in Molecular Match (advisor), OncoResponse (founder), and Presagia Inc (advisor). Yu Fujiwara has no disclosures. Publisher Copyright: {\textcopyright} 2022, Innovative Healthcare Institute. All rights reserved.",
year = "2022",
month = aug,
day = "1",
doi = "10.36401/JIPO-22-5",
language = "English (US)",
volume = "5",
pages = "68--78",
journal = "Journal of Immunotherapy and Precision Oncology",
issn = "2666-2345",
publisher = "Innovative Healthcare Institute",
number = "3",
}