Cancer Therapy Utilizing the RAS Protein Family

The RAS protein family functions as binary switch proteins toggling between active (GTP-bound) and inactive (GDP-bound) states, regulating pivotal cellular pathways like PI3K, MAPK, and Ral-GEF. Dysregulation of Ras signaling, often via mutations, leads to constitutive activation of downstream pathways, driving uncontrolled cell proliferation, a hallmark of cancer. Targeting aberrant Ras signaling pathways with small molecular inhibitors represents a promising therapeutic strategy in cancer treatment. This review examines three main approaches: Farnesyltransferase inhibitors (FTIs), upstream regulation of KRAS, and kinase inhibitors targeting RAS effector pathways. FTIs: inhibiting Ras activation, exhibit cytostatic effects on cancer cells, with clinical trials demonstrating promising activity in various cancer types. Sotorasib: a KRAS p.G12C inhibitor, shows efficacy in KRAS p.G12C-mutated cancers, including pancreatic and non-small cell lung cancers, highlighting its potential as a targeted therapy. Additionally, kinase inhibitors targeting RAS effector pathways demonstrate efficacy in preclinical and clinical settings, with recent advancements in identifying direct RAS inhibitors showing promising results. Despite challenges such as drug resistance, ongoing research aims to develop more effective inhibitors, offering hope for improved cancer therapies targeting RAS-driven malignancies.