title: Metabolic synthetic lethality in cancer therapy.
abstract: Our understanding of cancer has recently seen a major paradigm shift resulting in it being viewed as a metabolic disorder, and altered cellular metabolism being recognised as a hallmark of cancer. This concept was spurred by the findings that the oncogenic mutations driving tumorigenesis induce a reprogramming of cancer cell metabolism that is required for unrestrained growth and proliferation. The recent discovery that mutations in key mitochondrial enzymes play a causal role in tumorigenesis suggested that dysregulation of metabolism could also be a driver of tumorigenesis. These mutations induce profound adaptive metabolic alterations that are a prerequisite for the survival of the mutated cells. Because these metabolic events are specific to cancer cells, they offer an opportunity to develop new therapies that specifically target tumour cells without affecting healthy tissue. Here, we will describe recent developments in metabolism-based cancer therapy, in particular focusing on the concept of metabolic synthetic lethality. This article is part of a Special Issue entitled Mitochondria in Cancer, edited by Giuseppe Gasparre, Rodrigue Rossignol and Pierre Sonveaux.
authors.affiliation: Medical Research Council Cancer Unit, University of Cambridge, Hutchison/MRC Research Centre, Cambridge CB2 0XZ, United Kingdom.
authors.forename: Vincent
authors.initials: V
authors.lastname: Zecchini
authors.affiliation: Medical Research Council Cancer Unit, University of Cambridge, Hutchison/MRC Research Centre, Cambridge CB2 0XZ, United Kingdom. Electronic address: cf366@MRC-CU.cam.ac.uk.
authors.forename: Christian
authors.initials: C
authors.lastname: Frezza
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology* / Q000627:therapeutic use; D003198:Computer Simulation; D004734:Energy Metabolism / Q000187:drug effects* / Q000235:genetics; D005544:Forecasting; D018628:Gene Dosage; D020868:Gene Silencing; D052138:Genes, Neoplasm; D006801:Humans; D055442:Metabolome; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology; D008954:Models, Biological; D058990:Molecular Targeted Therapy; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000502:physiology; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D009857:Oncogenes; D010085:Oxidative Phosphorylation; D034622:RNA Interference; D000072020:Synthetic Lethal Mutations
chemical_list: D000964:Antimetabolites, Antineoplastic; D024101:Mitochondrial Proteins; D009363:Neoplasm Proteins