Journal Article (Review Article)

DKFZ-2025-00017

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png KRAS inhibitors: resistance drivers and combinatorial strategies.

Isermann, T.DKFZ* ; Sers, C.DKFZ* ; Der, C. J. ; Papke, B.DKFZ*

2025
Elsevier Amsterdam

This record in other databases:  

Please use a persistent id in citations: doi:10.1016/j.trecan.2024.11.009

Abstract: In 1982, the RAS genes HRAS and KRAS were discovered as the first human cancer genes, with KRAS later identified as one of the most frequently mutated oncogenes. Yet, it took nearly 40 years to develop clinically effective inhibitors for RAS-mutant cancers. The discovery in 2013 by Shokat and colleagues of a druggable pocket in KRAS paved the way to FDA approval of the first covalently binding KRASG12C inhibitors, sotorasib and adagrasib, in 2021 and 2022, respectively. However, rather than marking the end of a successful assault on the Mount Everest of cancer research, this landmark only revealed new challenges in RAS drug discovery. In this review, we highlight the progress on defining resistance mechanisms and developing combination treatment strategies to improve patient responses to KRAS therapies.

Keyword(s): KRAS ; colorectal carcinoma ; drug resistance ; non-small cell lung cancer ; pancreatic ductal adenocarcinoma

Note: 2025 Feb;11(2):91-116

---

Contributing Institute(s):

1. DKTK Koordinierungsstelle Berlin (BE01)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2024

---

Database coverage:
; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Essential Science Indicators ; IF >= 15 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---