Evgeny N Imyanitov, Natalia V Mitiushkina, Ekatherina Sh Kuligina, Vladislav I Tiurin, Aigul R Venina
{"title":"非小细胞肺癌中 BRAF 的作用途径和靶向途径。","authors":"Evgeny N Imyanitov, Natalia V Mitiushkina, Ekatherina Sh Kuligina, Vladislav I Tiurin, Aigul R Venina","doi":"10.1080/14728222.2024.2374742","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>BRAF is a serine-threonine kinase implicated in the regulation of MAPK signaling cascade. BRAF mutation-driven activation occurs in approximately 2-4% of treatment-naive non-small cell carcinomas (NSCLCs). BRAF upregulation is also often observed in tumors with acquired resistance to receptor tyrosine kinase inhibitors (TKIs).</p><p><strong>Areas covered: </strong>This review describes the spectrum of <i>BRAF</i> mutations and their functional roles, discusses treatment options available for <i>BRAF</i> p.V600 and non-V600 mutated NSCLCs, and identifies some gaps in the current knowledge.</p><p><strong>Expert opinion: </strong>Administration of combined BRAF/MEK inhibitors usually produces significant, although often a short-term, benefit to NSCLC patients with <i>BRAF</i> V600 (class 1) mutations. There are no established treatments for <i>BRAF</i> class 2 (L597, K601, G464, G469A/V/R/S, fusions, etc.) and class 3 (D594, G596, G466, etc.) mutants, which account for up to two-thirds of <i>BRAF</i>-driven NSCLCs. Many important issues related to the use of immune therapy for the management of <i>BRAF</i>-mutated NSCLC deserve further investigation. The rare occurrence of <i>BRAF</i> mutations in NSCLC is compensated by high overall incidence of lung cancer disease; therefore, clinical studies on <i>BRAF</i>-associated NSCLC are feasible.</p>","PeriodicalId":12185,"journal":{"name":"Expert Opinion on Therapeutic Targets","volume":" ","pages":"613-622"},"PeriodicalIF":4.6000,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Pathways and targeting avenues of BRAF in non-small cell lung cancer.\",\"authors\":\"Evgeny N Imyanitov, Natalia V Mitiushkina, Ekatherina Sh Kuligina, Vladislav I Tiurin, Aigul R Venina\",\"doi\":\"10.1080/14728222.2024.2374742\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>BRAF is a serine-threonine kinase implicated in the regulation of MAPK signaling cascade. BRAF mutation-driven activation occurs in approximately 2-4% of treatment-naive non-small cell carcinomas (NSCLCs). BRAF upregulation is also often observed in tumors with acquired resistance to receptor tyrosine kinase inhibitors (TKIs).</p><p><strong>Areas covered: </strong>This review describes the spectrum of <i>BRAF</i> mutations and their functional roles, discusses treatment options available for <i>BRAF</i> p.V600 and non-V600 mutated NSCLCs, and identifies some gaps in the current knowledge.</p><p><strong>Expert opinion: </strong>Administration of combined BRAF/MEK inhibitors usually produces significant, although often a short-term, benefit to NSCLC patients with <i>BRAF</i> V600 (class 1) mutations. There are no established treatments for <i>BRAF</i> class 2 (L597, K601, G464, G469A/V/R/S, fusions, etc.) and class 3 (D594, G596, G466, etc.) mutants, which account for up to two-thirds of <i>BRAF</i>-driven NSCLCs. Many important issues related to the use of immune therapy for the management of <i>BRAF</i>-mutated NSCLC deserve further investigation. The rare occurrence of <i>BRAF</i> mutations in NSCLC is compensated by high overall incidence of lung cancer disease; therefore, clinical studies on <i>BRAF</i>-associated NSCLC are feasible.</p>\",\"PeriodicalId\":12185,\"journal\":{\"name\":\"Expert Opinion on Therapeutic Targets\",\"volume\":\" \",\"pages\":\"613-622\"},\"PeriodicalIF\":4.6000,\"publicationDate\":\"2024-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Expert Opinion on Therapeutic Targets\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/14728222.2024.2374742\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/7/4 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Expert Opinion on Therapeutic Targets","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/14728222.2024.2374742","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/7/4 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Pathways and targeting avenues of BRAF in non-small cell lung cancer.
Introduction: BRAF is a serine-threonine kinase implicated in the regulation of MAPK signaling cascade. BRAF mutation-driven activation occurs in approximately 2-4% of treatment-naive non-small cell carcinomas (NSCLCs). BRAF upregulation is also often observed in tumors with acquired resistance to receptor tyrosine kinase inhibitors (TKIs).
Areas covered: This review describes the spectrum of BRAF mutations and their functional roles, discusses treatment options available for BRAF p.V600 and non-V600 mutated NSCLCs, and identifies some gaps in the current knowledge.
Expert opinion: Administration of combined BRAF/MEK inhibitors usually produces significant, although often a short-term, benefit to NSCLC patients with BRAF V600 (class 1) mutations. There are no established treatments for BRAF class 2 (L597, K601, G464, G469A/V/R/S, fusions, etc.) and class 3 (D594, G596, G466, etc.) mutants, which account for up to two-thirds of BRAF-driven NSCLCs. Many important issues related to the use of immune therapy for the management of BRAF-mutated NSCLC deserve further investigation. The rare occurrence of BRAF mutations in NSCLC is compensated by high overall incidence of lung cancer disease; therefore, clinical studies on BRAF-associated NSCLC are feasible.
期刊介绍:
The journal evaluates molecules, signalling pathways, receptors and other therapeutic targets and their potential as candidates for drug development. Articles in this journal focus on the molecular level and early preclinical studies. Articles should not include clinical information including specific drugs and clinical trials.
The Editors welcome:
Reviews covering novel disease targets at the molecular level and information on early preclinical studies and their implications for future drug development.
Articles should not include clinical information including specific drugs and clinical trials.
Original research papers reporting results of target selection and validation studies and basic mechanism of action studies for investigative and marketed drugs.
The audience consists of scientists, managers and decision makers in the pharmaceutical industry, academic researchers working in the field of molecular medicine and others closely involved in R&D.