KRAS mutation subtypes (G12C, G12D, G12V)
KRAS, the most commonly mutated cancer gene, comes in flavours named by the exact amino acid change. G12C (common in smokers' lung cancer) was the first to get a drug; G12D dominates pancreatic and colorectal cancer and its inhibitors are arriving now.
KRAS is mutated in about 90% of pancreatic, 40% of colorectal and 30% of lung adenocarcinomas. The G12C variant (13% of lung adenocarcinoma) is targeted by sotorasib and adagrasib, approved in 2021-22 with modest durability; G12D (40% of pancreatic cancer) is the target of zoldonrasib and others; daraxonrasib and related RAS(ON) multi-selective inhibitors cover several variants and produced the first positive phase 3 in pancreatic cancer. Variant also predicts behaviour: G12C lung tumours are smoking-related and immunogenic, while colorectal KRAS mutations of any type preclude EGFR antibodies. Co-mutations (STK11, KEAP1, TP53) modify prognosis and immunotherapy benefit.
Pages like this
not linked directly; found by shared links- PersonKevan M. Shokat
Shares Adagrasib, Sotorasib, KRAS & RAS inhibitors, KRAS.
- Key paperOstrem and Shokat: the hidden pocket that made KRAS G12C druggable
Shares Adagrasib, Sotorasib, KRAS & RAS inhibitors, KRAS.
- IdeaCovalent chemistry for the RAS mutations that still have no drug
Shares Adagrasib, Sotorasib, KRAS & RAS inhibitors, KRAS.
- RoadmapKRAS roadmap: undruggable → G12C → pan-RAS
Shares Adagrasib, Sotorasib, KRAS & RAS inhibitors, KRAS.
- TrialKrascendo 1
Shares Adagrasib, Sotorasib, KRAS, Non-small-cell lung cancer.
- ProductOlomorasib
Shares KRAS & RAS inhibitors, KRAS, Pancreatic ductal adenocarcinoma, Colorectal cancer.
- ProductElironrasib
Shares KRAS & RAS inhibitors, KRAS, Pancreatic ductal adenocarcinoma, Colorectal cancer.
- PairingKRAS G12C inhibitor + anti-EGFR antibody (colorectal)
Shares Adagrasib, Sotorasib, KRAS & RAS inhibitors, Colorectal cancer.