Figure 1.

A schema of the RAS-RAF-MEK-ERK pathway, the immune microenvironment in RAS-mutant cancer, and potential therapeutic strategies targeting RAS-mutant cancer. Oncogenic RAS signaling promotes PD-L1 expression through stabilization of PD-L1 mRNA, leading to immune escape in the tumor microenvironment. The inhibitors of the RAS-RAF-MEK-ERK pathway and the RAS-PI3K-AKT-mTOR pathway are potential agents to improve survival outcomes in patients with RAS mutations. *Tipifarnib is a farnesyltransferase inhibitor and demonstrated encouraging efficacy (objective response rate: 55%) in patients with head and neck squamous cell carcinoma harboring HRAS mutations.

AKT: protein kinase B; CDK: cyclin-dependent kinase; CTLA-4: cytotoxic T-lymphocyte–associated antigen 4; EGFR: epithelial growth factor receptor; ERK: extracellular signal regulated kinase; GDP: guanosine diphosphate; GTP: guanosine triphosphate; HRAS: Harvey rat sarcoma virus oncogene; KRAS: Kirsten rat sarcoma viral oncogene homologue; MEK: mitogen-activated protein kinase; MHC-1: major histocompatibility class I; mRNA: messenger RNA; mTOR: mammalian target of rapamycin; NRAS: neuroblastoma rat sarcoma virus oncogene; PD-1: programmed cell death 1; PD-L1: programmed death-ligand 1; PI3K: phosphatidylinositol 3-kinase; RAF: rapidly accelerated fibrosarcoma; RAS: rat sarcoma virus oncogene; RNA: ribonucleic acid; RTK: receptor tyrosine kinase; SHP2: Src homology 2 domain-containing protein tyrosine phosphatase-2; SOS1: Son of sevenless 1; TCR: T-cell receptor; TKI: tyrosine kinase inhibitor.