Year: 2025
Type: editorial
Abstract: The belief that RAS was “undruggable,” once etched in stone, was shattered with the first clinical approval of KRASG12C inhibitors in 2021 and 2022. Since then, numerous RAS inhibitors that target different oncogenic mutations, including pan-RAS approaches, have entered clinical trials. However, colorectal cancer (CRC) poses a significant therapeutic challenge for RAS inhibition due to robust feedback loops and compensatory receptor tyrosine kinase (RTK) activation, similar to resistance mechanisms previously observed in the early years of BRAF inhibitor clinical development. Consequently, combination therapy with EGFR inhibitors is essential to counteract these adaptive responses, an approach recently validated for KRASG12C inhibitors. Nevertheless, responses to the combination of KRASG12C inhibitors with EGFR antibodies remain incomplete, and resistance typically develops with a progression free survival of approximately 7 months.
DOI: 10.1002/ueg2.70138
Authors: Bjoern Papke, Channing J. Der
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $2,930
Awards: G1319661684, G2221353213, Biological Activity of Ras Oncogenes, Defining RAS isoform- and mutation-specific roles in oncogenesis, Targeting undruggable RAS for cancer treatment, Washington University SPORE in Pancreatic Cancer, G5028106406, Identification of synthetic lethal interactors in pancreatic cancer, TARGETING KRAS-DYSREGULATED METABOLISM FOR NOVEL THERAPEUTIC APPROACHES, Selective Targeting of Pancreatic Cancer SPORE
OpenAlex ID: W4415378274