Aug 2026· Oncogene· Vol 45, pp. 4191 - 4201· 0 citations· 65 references
Medicine
TL;DR
These findings establish RAF1 S257L/S259F as critical determinants of MAPK pathway activation and cellular response under daraxonrasib, provide mechanistic insights into intrinsic resistance to RAS(ON) inhibition, and underscore a therapeutic framework for genotype-guided combination strategies in RAF1-mutant melanoma.
Metastatic melanoma remains highly lethal despite advances in immunotherapy and MAPK-targeted therapy. The Rac1P29S mutation, present in 4-9% of cutaneous melanomas, confers intrinsic resistance to BRAF and MEK inhibitors. Like other small GTPases, Rac1 lacks suitable pockets for small molecule inhibitor binding, motiv...
S. E. Simon, Tian-Nan Wang, Arsha Sreekumar et al.· bioRxiv· 0 citations
Pancreatic ductal adenocarcinoma (PDAC) is projected to become the second leading cause of cancer death in the United States by 2040. Oncogenic KRAS, present in ∼90% of PDACs, drives tumor growth through MAPK signaling and ERK1/2 activation. While pan-RAS and mutant-selective KRAS inhibitors can produce initial r...
Luisa F. Escobar-Hoyos, Md Siraj Afjalus, Deanne E. Yugawa et al.· Cancer Research· 0 citations
Inhibiting pan-RAS(on) RAS-GTP with daraxonrasib, alone or in combination with a MEK inhibitor, provides a new strategy for the treatment of TNBC that inhibits RTK activation of the RAS-RAF-MEK-ERK pathway and tumor proliferation.
Michael P. East, J. Olivares-Quintero, D. Okumu et al.· bioRxiv· 0 citations
The efficacy of immune checkpoint blockade (ICB) in lung adenocarcinoma (LUAD) is limited by primary or acquired resistance, especially in genetically defined subsets. We investigated the impact of KRAS/TP53 co-mutation on ICB response. Our analysis reveals that KRAS/TP53 co-mutation is associated with favorable ICB ou...
Xin Zhang, Q. Hao, Wen-Yue Yang et al.· Science Advances· 0 citations
The obtained results suggest that the purpose of metabolic changes present in melanoma cells resistant to BRAF/MEK inhibitors is mainly to support the significantly increased invasiveness of these cells.
M. Kot, A. Simiczyjew, Katarzyna Pietraszek-Gremplewicz et al.· Biochimica et biophysica act...· 0 citations
Intraductal Papillary Mucinous Neoplasm (IPMN) are pre-malignant lesions of the pancreas with frequent co-mutations in KRAS and GNAS oncogenes. We recently reported pancreatic neoplasia from both primary and metastatic disease with KRAS/GNAS mutations are sensitive to single agent treatment with the FDA approved cell...
Deepa Sheik Pran Babu, Shira Yomtoubian, Ethan Tabibzadeh et al.· Cancer Research· 0 citations
We use cookies to run the site and, with your consent, for analytics and to show ads.
See our Cookie Policy.
