Year: 2024
Type: article
Abstract: Summary Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with a poor 5‑year survival rate. The majority of PDAC cases harbor KRAS mutations, predominantly at codon 12, with G12D being the most common. While selective inhibitors like sotorasib have shown promise in KRASG12C-mutated PDAC, these mutations are rare, and resistance develops rapidly. Efforts to target more prevalent mutations like KRASG12D are ongoing, with compounds such as MRTX1133 showing preclinical efficacy. Resistance mechanisms include secondary mutations and pathway reactivation, prompting the development of pan-(K)RAS inhibitors (e.g., RMC-6236) and combination strategies targeting upstream effectors. Novel approaches, such as KRAS-targeted vaccines and T‑cell receptor (TCR) therapies, offer additional potential. Continued clinical trials are crucial to optimizing KRAS-targeted therapies in PDAC.
Author: Bernhard Doleschal
Institution: Johannes Kepler University of Linz
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,590
OpenAlex ID: W4404586667