BRAF和MEK抑制剂治疗BRAF突变癌症的精准治疗：从黑色素瘤到组织非特异性治疗。
Precision oncology for BRAF-mutant cancers with BRAF and MEK inhibitors: from melanoma to tissue-agnostic therapy.
发表日期：2023 Feb 24
作者：
M A Gouda, V Subbiah
来源：
ESMO Open
摘要：
BRAF激活作为有丝分裂原激活蛋白激酶（MAPK）细胞信号通路的一部分，会导致细胞增殖和存活增加。 BRAF的突变可以导致下游激酶的放任活化，随后导致无法控制的细胞生长，形成多种肿瘤的致癌基础。通过选择性抑制剂靶向BRAF已成为精准肿瘤学的早期成功之一。在BRAF V600突变的多种肿瘤中，探索了代理单一治疗或与MEK抑制剂结合治疗，并与EGFR抑制剂结合治疗结直肠癌。 BRAF抑制剂的范围已从仅限黑色素瘤演变为普遍的肿瘤靶标。在本文中，我们回顾了BRAF和MEK抑制剂药物从组织特异性黑色素瘤，非小细胞肺癌和间变性甲状腺癌到组织不加限制批准的发展历程。版权所有©2023作者出版Elsevier Ltd.。保留所有权利。
BRAF activation occurs as part of the mitogen-activated protein kinase (MAPK) cellular signaling pathway which leads to increased cellular proliferation and survival. Mutations in BRAF can result in unbridled activation of downstream kinases with subsequent uncontrolled cellular growth that formulate the basis for oncogenesis in multiple tumor types. Targeting BRAF by selective inhibitors has been one of the early successes in precision oncology. Agents have been explored either as monotherapy or in combination with MEK inhibition in BRAF V600-mutant pan-cancers and with EGFR inhibition in colorectal cancer. Spectrum of BRAF inhibition has evolved from being melanoma-specific to being a pan-cancer target. In this article, we review BRAF and MEK inhibitor drug development journey from tissue-specific melanoma, non-small-cell lung cancer, and anaplastic thyroid cancer to tissue-agnostic approvals.Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.