title: Role of AKT signaling in DNA repair and clinical response to cancer therapy.
abstract: Effective cancer treatment has been limited by the emergence of resistant cancer cells. The results of many studies indicate that AKT activation plays an important role in the acquisition of resistance to anticancer therapy. AKT is a critical effector serine/threonine kinase in the receptor tyrosine kinase/phosphatase and tensin homolog/phospho-inositide 3-kinase pathway and controls a myriad of cellular functions. Activation of AKT not only supports tumor growth and progression but also contributes to tumor-cell evasion of the cytotoxic effects of cancer therapy through many avenues including the promotion of anti-apoptosis, proliferation, and migration and regulation of the cell cycle. Accumulating evidence has implicated AKT as a direct participant in the DNA damage response and repair induced by commonly used genotoxic agents. In this review, we discuss the molecular mechanisms by which genotoxic agents activate AKT and therefore contribute to resistance to cancer therapeutics, with particular emphasis on DNA repair.
authors.affiliation: Department of Neuro-Oncology, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China (Q.L.); Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas (K.M.T., W.Z.); Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (W.K.A.Y.); Department of Epidemiology and Biostatistics, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China (K.C.).
authors.forename: Qun
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Neuro-Oncology, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China (Q.L.); Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas (K.M.T., W.Z.); Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (W.K.A.Y.); Department of Epidemiology and Biostatistics, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China (K.C.).
authors.forename: Kristen M
authors.initials: KM
authors.lastname: Turner
authors.affiliation: Department of Neuro-Oncology, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China (Q.L.); Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas (K.M.T., W.Z.); Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (W.K.A.Y.); Department of Epidemiology and Biostatistics, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China (K.C.).
authors.forename: W K
authors.initials: WK
authors.lastname: Alfred Yung
authors.affiliation: Department of Neuro-Oncology, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China (Q.L.); Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas (K.M.T., W.Z.); Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (W.K.A.Y.); Department of Epidemiology and Biostatistics, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China (K.C.).
authors.forename: Kexin
authors.initials: K
authors.lastname: Chen
authors.affiliation: Department of Neuro-Oncology, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China (Q.L.); Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas (K.M.T., W.Z.); Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (W.K.A.Y.); Department of Epidemiology and Biostatistics, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China (K.C.).
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000818:Animals; D004249:DNA Damage; D004260:DNA Repair; D019008:Drug Resistance, Neoplasm; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics*; D015398:Signal Transduction
chemical_list: D051057:Proto-Oncogene Proteins c-akt
keywords: DNA damage; DNA repair: AKT; cancer; treatment resistance