PI3K/AKT/mTOR pathway,hypoxia,and glucose metabolism:Potential targets to overcome radioresistance in small cell lung cancer

作     者：Huan Deng Yamei Chen Peijing Li Qingqing Hang Peng Zhang Ying Jin Ming Chen Huan Deng;Yamei Chen;Peijing Li;Qingqing Hang;Peng Zhang;Ying Jin;Ming Chen

作者机构：Department of Medical OncologyThe Cancer Hospital of the University of Chinese Academy of Sciences(Zhejiang Cancer Hospital)HangzhouZhejiang 310022China Department of Radiation OncologyZhejiang Key Laboratory of Radiation OncologyHangzhouZhejiang 310022China Department of Radiation OncologyInstitute of Basic Medicine and Cancer(IBMC)Chinese Academy of SciencesHangzhouZhejiang 310022China College of Life SciencesUniversity of the Chinese Academy of SciencesBeijing 100049China Department of Radiation OncologySun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineSun Yat-sen UniversityGuangzhouGuangdong 510060China 

出 版 物：《Cancer Pathogenesis and Therapy》 (癌症发生与治疗（英文）)

年 卷 期：2023年第1卷第1期

页      面：56-66页

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：This study is supported by the National Natural Science Foundation of China(No.81672972) 

主　　题：Small cell lung cancer PI3K/AKT/mTOR pathway Glucose metabolism Radioresistance 

摘      要：Small cell lung cancer(SCLC)is a highly aggressive tumor type for which limited therapeutic progress has been ***-based chemotherapy with or without thoracic radiotherapy remains the backbone of treatment,but most patients with SCLC acquire therapeutic *** the need for more effective therapies,better elucidation of the molecular pathogenesis of SCLC is *** phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)/mammalian target of rapamycin(mTOR)pathway is frequently activated in SCLC and strongly associated with resistance to ionizing radiation in many solid *** pathway is an important regulator of cancer cell glucose metabolism,and its activation probably effects radioresistance by influencing bioenergetic processes in *** metabolism has three main branches-aerobic glycolysis,oxidative phosphorylation,and the pentose phosphate pathway-involved in *** interaction between the PI3K/AKT/mTOR pathway and glucose metabolism is largely mediated by hypoxia-inducible factor 1(HIF-1)*** PI3K/AKT/mTOR pathway also influences glucose metabolism through other mechanisms to participate in radioresistance,including inhibiting the ubiquitination of rate-limiting enzymes of the pentose phosphate *** review summarizes our understanding of links among the PI3K/AKT/mTOR pathway,hypoxia,and glucose metabolism in SCLC radioresistance and highlights promising research directions to promote cancer cell death and improve the clinical outcome of patients with this devastating disease.