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Metabolic synthetic lethality in cancer therapy

Accepted version
Peer-reviewed

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Type

Article

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Authors

Zecchini, Vincent 

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.

Description

Keywords

Antimetabolites, Antineoplastic, Computer Simulation, Energy Metabolism, Forecasting, Gene Dosage, Gene Silencing, Genes, Neoplasm, Humans, Metabolome, Mitochondria, Mitochondrial Proteins, Models, Biological, Molecular Targeted Therapy, Neoplasm Proteins, Neoplasms, Oncogenes, Oxidative Phosphorylation, RNA Interference, Synthetic Lethal Mutations

Journal Title

Biochimica et Biophysica Acta (BBA) - Bioenergetics

Conference Name

Journal ISSN

0005-2728
1879-2650

Volume Title

1858

Publisher

Elsevier
Sponsorship
MRC (unknown)
Worldwide Cancer Research (formerly AICR) (14-0319)
VZ is supported by the Worldwide Cancer Research (WCR, formerly known as AICR). CF receives support from the Medical Research Council, core fund to the MRC Cancer Unit.