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Tumours with class 3 BRAF mutants are sensitive to the inhibition of activated RAS.
Yao Z, Yaeger R, Rodrik-Outmezguine VS, Tao A, Torres NM, Chang MT, Drosten M, Zhao H, Cecchi F, Hembrough T, Michels J, Baumert H, Miles L, Campbell NM, de Stanchina E, Solit DB, Barbacid M, Taylor BS, Rosen N. Yao Z, et al. Nature. 2017 Aug 10;548(7666):234-238. doi: 10.1038/nature23291. Epub 2017 Aug 2. Nature. 2017. PMID: 28783719 Free PMC article.
The mutants bind more tightly than wild-type BRAF to RAS-GTP, and their binding to and activation of wild-type CRAF is enhanced, leading to increased ERK signalling. The model suggests that dysregulation of signalling by these mutants in tumours requires coexistent mechani …
The mutants bind more tightly than wild-type BRAF to RAS-GTP, and their binding to and activation of wild-type CRAF is enhanced, lead …
RAF1 kinase activity is dispensable for KRAS/p53 mutant lung tumor progression.
Sanclemente M, Nieto P, Garcia-Alonso S, Fernández-García F, Esteban-Burgos L, Guerra C, Drosten M, Caleiras E, Martinez-Torrecuadrada J, Santamaría D, Musteanu M, Barbacid M. Sanclemente M, et al. Cancer Cell. 2021 Mar 8;39(3):294-296. doi: 10.1016/j.ccell.2021.01.008. Epub 2021 Jan 28. Cancer Cell. 2021. PMID: 33513349 Free article. No abstract available.
c-Raf in KRas Mutant Cancers: A Moving Target.
McCormick F. McCormick F. Cancer Cell. 2018 Feb 12;33(2):158-159. doi: 10.1016/j.ccell.2018.01.017. Cancer Cell. 2018. PMID: 29438690 Free PMC article.
In the current issue of Cancer Cell, Sanclemente and coworkers in Mariano Barbacid's group validate c-Raf as a prime target for these cancers. c-Raf ablation caused regression of advanced KRas(G12V)/Trp53 tumors, without obvious systemic toxicity and without affecting MAPK …
In the current issue of Cancer Cell, Sanclemente and coworkers in Mariano Barbacid's group validate c-Raf as a prime target for these …
A Braf kinase-inactive mutant induces lung adenocarcinoma.
Nieto P, Ambrogio C, Esteban-Burgos L, Gómez-López G, Blasco MT, Yao Z, Marais R, Rosen N, Chiarle R, Pisano DG, Barbacid M, Santamaría D. Nieto P, et al. Nature. 2017 Aug 10;548(7666):239-243. doi: 10.1038/nature23297. Epub 2017 Aug 2. Nature. 2017. PMID: 28783725 Free PMC article.
Co-expression of Kras(G12V) and Braf(D631A) in mouse lung cells markedly enhances tumour initiation, a phenomenon mediated by Craf kinase activity, and effectively accelerates tumour progression when activated in advanced lung adenocarcinomas. ...
Co-expression of Kras(G12V) and Braf(D631A) in mouse lung cells markedly enhances tumour initiation, a phenomenon mediated by Craf ki …
Complete Regression of Advanced Pancreatic Ductal Adenocarcinomas upon Combined Inhibition of EGFR and C-RAF.
Blasco MT, Navas C, Martín-Serrano G, Graña-Castro O, Lechuga CG, Martín-Díaz L, Djurec M, Li J, Morales-Cacho L, Esteban-Burgos L, Perales-Patón J, Bousquet-Mur E, Castellano E, Jacob HKC, Cabras L, Musteanu M, Drosten M, Ortega S, Mulero F, Sainz B Jr, Dusetti N, Iovanna J, Sánchez-Bueno F, Hidalgo M, Khiabanian H, Rabadán R, Al-Shahrour F, Guerra C, Barbacid M. Blasco MT, et al. Cancer Cell. 2019 Apr 15;35(4):573-587.e6. doi: 10.1016/j.ccell.2019.03.002. Epub 2019 Apr 8. Cancer Cell. 2019. PMID: 30975481 Free PMC article.
RAF inhibitor PLX8394 selectively disrupts BRAF dimers and RAS-independent BRAF-mutant-driven signaling.
Yao Z, Gao Y, Su W, Yaeger R, Tao J, Na N, Zhang Y, Zhang C, Rymar A, Tao A, Timaul NM, Mcgriskin R, Outmezguine NA, Zhao H, Chang Q, Qeriqi B, Barbacid M, de Stanchina E, Hyman DM, Bollag G, Rosen N. Yao Z, et al. Nat Med. 2019 Feb;25(2):284-291. doi: 10.1038/s41591-018-0274-5. Epub 2018 Dec 17. Nat Med. 2019. PMID: 30559419 Free PMC article.
We show here that PLX8394, a new RAF inhibitor(9), inhibits ERK signaling by specifically disrupting BRAF-containing dimers, including BRAF homodimers and BRAF-CRAF heterodimers, but not CRAF homodimers or ARAF-containing dimers. Differences in the amino acid residu …
We show here that PLX8394, a new RAF inhibitor(9), inhibits ERK signaling by specifically disrupting BRAF-containing dimers, including BRAF …