Resistance to immune checkpoint inhibitors in KRAS-mutant non-small cell lung cancer

Yunchang Li; Lanlin Hu; Xinhao Peng; Huasheng Xu; Bo Tang; Chuan Xu

doi:10.20517/cdr.2021.102

Resistance to immune checkpoint inhibitors in KRAS-mutant non-small cell lung cancer

Cancer Drug Resist. 2022 Feb 8;5(1):129-146. doi: 10.20517/cdr.2021.102. eCollection 2022.

Authors

Yunchang Li^{1

2}, Lanlin Hu^{1

2}, Xinhao Peng¹, Huasheng Xu³, Bo Tang¹, Chuan Xu¹

Affiliations

¹ Integrative Cancer Center and Cancer Clinical Research Center, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610042, Sichuan, China.
² Authors contributed equally.
³ Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application, Guangxi Medical University, Nanning 530021, Guangxi, China.

Abstract

Non-small cell lung cancer (NSCLC) patients with Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation are associated with significant clinical heterogeneity and a poor prognosis to standard NSCLC therapies such as surgical resection, radiotherapy, chemotherapies, and targeted medicines. However, the application of immune checkpoints inhibitors (ICIs) has dramatically altered the therapeutic pattern of NSCLC management. Clinical studies have indicated that some KRAS-mutant NSCLC patients could benefit from ICIs; however, the responses in some patients are still poor. This review intends to elucidate the mechanisms of resistance to immunotherapy in KRAS-driven NSCLC and highlight the TME functions altered by immunoinhibitors, immunostimulators, and cancer metabolism. These metabolic pathways could potentially be promising approaches to overcome immunotherapy resistance.

Keywords: KRAS mutation; Non-small cell lung cancer; cancer metabolism.; immune checkpoints inhibitors; tumor microenvironments.

Publication types

Review