Evaluation of KRAS inhibitor-directed therapies for pancreatic cancer treatment

• DOI: 10.3389/fonc.2024.1402128
• Publication Date: 2024-05-10T04:22:27Z
• Authors: Szu-Aun Long; Amber M. Amparo; Grace Goodhart; Syed A. Ahmad; Andrew M. Waters
• Keywords: Targeted Therapy

Despite significant advancements in the treatment of other cancers, pancreatic ductal adenocarcinoma (PDAC) remains one world’s deadliest cancers. More than 90% PDAC patients harbor a Kirsten rat sarcoma (KRAS) gene mutation. Although clinical potential anti-KRAS therapies has long been realized, all initial efforts to target KRAS were unsuccessful. However, with recent development new generation KRAS-targeting drugs, multiple KRAS-targeted options for have entered trials. In this review, we provide an overview current standard care treatment, describe RAS signaling and relevance mutations, discuss isoform- mutation-specific differences. We also evaluate efficacy safety mutation-selective multi-selective inhibitors, context PDAC. then comparison clinically relevant inhibitors second-line options. Finally, putative resistance mechanisms that may limit effectiveness brief promising therapeutic approaches are focused on mitigating these mechanisms.