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International review of cell and molecular biology, 2021, Vol.364, p.241
Ort / Verlag
Netherlands
Erscheinungsjahr
2021
Link zum Volltext
Quelle
MEDLINE
Beschreibungen/Notizen
Genomic instability and metabolic reprogramming are among the key hallmarks discriminating cancer cells from normal cells. The two phenomena contribute to the robust and evasive nature of cancer, particularly when cancer cells are exposed to chemotherapeutic agents. Genomic instability is defined as the increased frequency of mutations within the genome, while metabolic reprogramming is the alteration of metabolic pathways that cancer cells undergo to adapt to increased bioenergetic demand. An underlying source of these mutations is the aggregate product of damage to the DNA, and a defective repair pathway, both resulting in the expansion of genomic lesions prior to uncontrolled proliferation and survival of cancer cells. Exploitation of DNA damage and the subsequent DNA damage response (DDR) have aided in defining therapeutic approaches in cancer. Studies have demonstrated that targeting metabolic reprograming yields increased sensitivity to chemo- and radiotherapies. In the past decade, it has been shown that these two key features are interrelated. Metabolism impacts DNA damage and DDR via regulation of metabolite pools. Conversely, DDR affects the response of metabolic pathways to therapeutic agents. Because of the interplay between genomic instability and metabolic reprogramming, we have compiled findings which more selectively highlight the dialog between metabolism and DDR, with a particular focus on glucose metabolism and double-strand break (DSB) repair pathways. Decoding this dialog will provide significant clues for developing combination cancer therapies.