title: EGFR signaling and autophagy dependence for growth, survival, and therapy resistance.
abstract: The epidermal growth factor receptor (EGFR) is amplified or mutated in various human epithelial tumors. Its expression and activation leads to cell proliferation, differentiation, and survival. Consistently, EGFR amplification or expression of EGFR variant 3 (EGFRvIII) is associated with resistance to conventional cancer therapy through activation of pro-survival signaling and DNA-repair mechanisms. EGFR targeting has successfully been exploited as strategy to increase treatment efficacy. Nevertheless, these targeting strategies have only been proven effective in a limited percentage of human tumors. Recent knowledge indicates that EGFR deregulated tumors display differences in autophagy and dependence on autophagy for growth and survival and the use of autophagy to increase resistance to EGFR-targeting drugs. In this review the dependency on autophagy and its role in mediating resistance to EGFR-targeting agents will be discussed. Considering the current knowledge, autophagy inhibition could provide a novel strategy to enhance therapy efficacy in treatment of EGFR deregulated tumors.
authors: Maastricht Radiation Oncology (MaastRO) Lab; GROW - School for Oncology and Developmental Biology; Maastricht University; Maastricht, the Netherlands.
authors: Barry
authors: B
authors: Jutten
authors: Maastricht Radiation Oncology (MaastRO) Lab; GROW - School for Oncology and Developmental Biology; Maastricht University; Maastricht, the Netherlands.
authors: Kasper M A
authors: KM
authors: Rouschop
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D001343:Autophagy / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D015398:Signal Transduction
chemical_list: D000970:Antineoplastic Agents; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: EGFR; EGFRvIII; autophagy; cancer treatment; hypoxia; metabolic stress; mutations; starvation; treatment resistance