title: Targeting AMPK Signaling Pathway to Overcome Drug Resistance for Cancer Therapy.
abstract: Mulitdrug resistance (MDR) is one of critical factorslimiting the efficacy of cancer chemoor radiotherapy. Emerging evidence has indicated that MDR is a complex process regulated by multiple factors, among which stress response molecules are considered as central players. AMP-activated protein kinase (AMPK) is a major regulator balancing energy supply and ultimately protects cells from harmful stresses via coordinating multiple metabolic pathways Notably, AMPK activation was recently shown to mediate the metabolism reprogramming in drug resistant cancer cells including promoting Warburg effects and mitochondrial biogenesis. Furthermore, AMPK activity has also been shown to regulate the self-renewal ability of cancer stem cells that are often refractory to chemotherapy. In addition, AMPK phosphorylation was critical in mediating autophagy induction, a process demonstrated to be effective in chemosensitivity modulation via degrading cellular components to satisfy nutrients requirement under stressful condition. Meanwhile, drug discovery targeting AMPK has been developed to validate the pathological significance of AMPK in cancer prevention and treatment. Although conflicting evidence focusing on the AMPK modulation for cancer treatment is still remained, this might be attributed to differences in AMPK isotypes in specific tissues, off-targets effects, the degree and duration of drug administration and experimental setting of stress conditions. This review will focus on AMPK mediated resistance to cancer therapy and discuss its potential therapeutic implication and targeting drug development.
authors.affiliation: Department of Mammary Disease, Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China. wangzhiyu976@126.com.
authors.forename: Zhiyu
authors.initials: Z
authors.lastname: Wang
authors.forename: Pengxi
authors.initials: P
authors.lastname: Liu
authors.forename: Qianjun
authors.initials: Q
authors.lastname: Chen
authors.forename: Shigui
authors.initials: S
authors.lastname: Deng
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Liu
authors.forename: Honglin
authors.initials: H
authors.lastname: Situ
authors.forename: Shaowen
authors.initials: S
authors.lastname: Zhong
authors.forename: Swei
authors.initials: S
authors.lastname: Hann
authors.forename: Yi
authors.initials: Y
authors.lastname: Lin
mesh_terms: D000263:Adenylate Kinase / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects; D055808:Drug Discovery; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D000263:Adenylate Kinase