摘要
目的总结能量代谢参与黑色素瘤靶向治疗耐药的相关研究,分析代谢表型转换调控黑色素瘤耐药的机制,探讨靶向代谢重编程对黑色素瘤药物敏感性的影响,为干预和延缓黑色素瘤耐药提供新思路。方法以“黑色素瘤、耐药、靶向治疗、代谢、MAPK通路、BRAF^(V600E)、BRAF^(V600K)、谷氨酰胺、线粒体、肿瘤微环境”为中文关键词,以“melanoma、resistance、targeted therapy、metabolism、MAPK pathway、BRAF^(V600E)、BRAF^(V600K)、glutamine、mitochondria、tumor microenvironment”为英文关键词,检索PubMed和中国知网数据库,共检索到中文文献23篇,英文文献548篇。纳入标准:(1)黑色素瘤流行病学、生物学和预后;(2)糖酵解参与黑色素瘤靶向耐药的机制;(3)代谢转换对黑色素瘤靶向耐药的影响。排除标准:(1)研究对象为黑色素瘤靶向治疗外的其他治疗方法;(2)会议论文、报告和信函等。根据标准共纳入文献61篇,中文2篇,英文59篇。结果临床使用靶向药物治疗黑色素瘤高效快速,毒副作用较小。但耐药性的发展限制了靶向药物的疗效,导致预后不良。在靶向治疗过程中,黑色素瘤主动调节代谢和供能方式,包括增强糖酵解和线粒体活性,增加谷氨酰胺分解,促进氧化磷酸化等方式,以维持细胞增殖,同时释放乳酸和CO_(2)等副产物,促进肿瘤微环境酸化,以进一步促进耐药发生。结论异常的能量代谢方式及伴随的肿瘤微环境酸化,是耐药黑色素瘤细胞赖以生存的重要因素,针对这些异常靶点进行干预,有望延缓黑色素瘤耐药发生。
Objective To summerize the research on energy metabolism involved in drug resistance in targeted therapy of melanoma,analyze the mechanisms by which metabolic phenotype switching in monitoring melanoma drug resistance,investigate the impact of targeted metabolic reprogramming on drug sensitivity by briefly compiling researches on the role of energy metabolism in targeted therapy resistance in melanoma and offering fresh perspectives for intervention and delay of drug resistance in melanoma.Methods PubMed and Chinese National Knowledge Infrastructure(CNKI) databases were retrieved,with the keywords of "melanoma,resistance,targeted therapy,metabolism,MAPK pathway,BRAF^(V600E),BRAF^(V600K),glutamine,mitochondria,and tmour microenvironment" in both Chinese and English.A total of 23 Chinese literature and 548 English literature were retrieved.The inclusion criteria were as follows:(1) melanoma epidemiology,biology,and prognosis;(2) glycolysis mechanism implicated in melanoma-targeted medication resistance;and(3) the effect of metabolic conversion on melanoma targeted therapy resistance.The exclusion criteria were as follows:(1)the subjects were other treatment methods besides targeted therapy for melanoma;(2)conference papers,reports,letters,etc.According to the requirements,63 papers were included,including 2 articles in Chinese and 59 articles in English.Results Targeted medication therapy for melanoma is efficacious,speedy,and has fewer adverse effects.But as drug resistance spreads,targeted pharmaceuticals get less potent,causing poor prognosis.In the process of targeted therapy,melanoma actively regulates metabolism and energy supply,including enhancing glycolysis and mitochondrial activity,increasing glutamine decomposition,promoting oxidative phosphorylation,in order to maintain cell proliferation,release lactic acid and CO_(2) and other byproducts,promote tumor microenvironment acidification,and further promote drug resistance during targeted therapy.Conclusions Interventions targeting these atypical targets are envisaged to delay the emergence of drug resistance in melanoma.Abnormal energy metabolism patterns and contemporaneous acidification of the tumor microenvironment are significant variables on which drug-resistant melanoma cells depend.
作者
林紫均
阮杰
刘新光
孙雪荣
LIN Zijun;RUAN Jie;LIU Xinguang;SUN Xuerong(Institute of Aging,Guangdong Key Laboratory of Medical Molecular Diagnosis,Guangdong Medical University,Dongguan,Guangdong 523808,China;College of Medical Technology,Guangdong Medical University,Dongguan,Guangdong 523808,China;Institute of Biochemistry and Molecular Biology,Affiliated Guangdong Medical University,Zhanjiang,Guangdong 524000,China)
出处
《中华肿瘤防治杂志》
CAS
北大核心
2023年第21期1320-1326,共7页
Chinese Journal of Cancer Prevention and Treatment
基金
广东省自然科学基金(2020A1515010026,2021A1515012236)
广东省中医药局中医药科研项目(20232096)
湛江市科技发展专项资金竞争性分配项目(2020A01033)
广东医科大学学科建设类专项项目(4SG23287G)。
关键词
黑色素瘤
耐药
糖酵解
谷氨酰胺
线粒体
肿瘤微环境
综述文献
melanoma
drug resistance
glycolysis
glutamine
mitochondria
tumor microenvironment
review literature
作者简介
第一作者:林紫均,女,广东恩平人,硕士,主要从事黑色素瘤靶向治疗耐药的研究工作。E-mail:linzijun1103@163.com;通信作者:孙雪荣,男,湖北赤壁人,副教授,主要从事黑色素瘤靶向治疗耐药以及细胞衰老的研究工作。E-mail:xuerongsun@126.com。
