title: Targeting mitochondrial metabolism by inhibiting autophagy in BRAF-driven cancers.
abstract: Metabolomic analyses of human tumors and mouse models of cancer have identified key roles for autophagy in supporting mitochondrial metabolism and homeostasis. In this review, we highlight data suggesting that autophagy inhibition may be particularly effective in BRAF-driven malignancies. Catalytic BRAF inhibitors have profound efficacy in tumors carrying activating mutations in Braf but are limited by the rapid emergence of resistance due in part to increased mitochondrial biogenesis and heightened rates of oxidative phosphorylation. We suggest that combined inhibition of autophagy and BRAF may overcome this limitation.
  
  
  CONCLUSIONS
  Braf(V600E)-driven tumors require autophagy and likely autophagy-provided substrates to maintain mitochondrial metabolism and to promote tumor growth, suggesting that autophagy ablation may improve cancer therapy.
authors.affiliation: Authors' Affiliations:Rutgers Cancer Institute of New Jersey, New Brunswick; and.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Strohecker
authors.affiliation: Authors' Affiliations:Rutgers Cancer Institute of New Jersey, New Brunswick; and Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey epwhite@cinj.rutgers.edu.
authors.forename: Eileen
authors.initials: E
authors.lastname: White
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols; D001343:Autophagy / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D009369:Neoplasms / Q000188:drug therapy*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D048493:Proto-Oncogene Proteins B-raf