首页|Targeting RAF dimers in RAS mutant tumors:From biology to clinic
Targeting RAF dimers in RAS mutant tumors:From biology to clinic
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RAS mutations occur in approximately 30％of tumors worldwide and have a poor prognosis due to limited therapies.Covalent targeting of KRAS G12C has achieved significant success in recent years,but there is still a lack of efficient therapeutic approaches for tumors with non-G12C KRAS mu-tations.A highly promising approach is to target the MAPK pathway downstream of RAS,with a partic-ular focus on RAF kinases.First-generation RAF inhibitors have been authorized to treat BRAF mutant tumors for over a decade.However,their use in RAS-mutated tumors is not recommended due to the par-adoxical ERK activation mainly caused by RAF dimerization.To address the issue of RAF dimerization,type Ⅱ RAF inhibitors have emerged as leading candidates.Recent clinical studies have shown the initial effectiveness of these agents against RAS mutant tumors.Promisingly,type Ⅱ RAF inhibitors in combi-nation with MEK or ERK inhibitors have demonstrated impressive efficacy in RAS mutant tumors.This review aims to clarify the importance of RAF dimerization in cellular signaling and resistance to treat-ment in tumors with RAS mutations,as well as recent progress in therapeutic approaches to address the problem of RAF dimerization in RAS mutant tumors.
Division of Abdominal Cancer,Department of Medical Oncology,Cancer Center and Laboratory of Molecular Targeted Therapy in Oncology,West China Hospital,Sichuan University,Chengdu 610041,China
国家自然科学基金国家自然科学基金四川省科技计划Sichuan University Postdoctoral Interdisciplinary Innovation Fund,China
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