One-carbon metabolism and nucleotide biosynthesis as attractive targets for anticancer therapy
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Oleg Shuvalov1, Alexey Petukhov1,2, Alexandra Daks1, Olga Fedorova1, Elena Vasileva1, Nickolai A. Barlev1
1Institute of Cytology RAS, Saint-Petersburg, Russian Federation
2Institute of Hematology, Almazov Federal North-West Medical Research Centre, Saint-Petersburg, Russian Federation
Oleg Shuvalov, email: [email protected]
Nickolai A. Barlev, email: [email protected]
Keywords: cancer metabolism, one-carbon metabolism, anti-cancer therapy, c-Myc, p53
Received: October 19, 2016 Accepted: December 02, 2016 Published: February 03, 2017
Cancer-related metabolism has recently emerged as one of the “hallmarks of cancer”. It has several important features, including altered metabolism of glucose and glutamine. Importantly, altered cancer metabolism connects different biochemical pathways into the one fine-tuned metabolic network, which stimulates high proliferation rates and plasticity to malignant cells. Among the keystones of cancer metabolism are one-carbon metabolism and nucleotide biosynthesis, which provide building blocks to anabolic reactions. Accordingly, the importance of these metabolic pathways for anticancer therapy has well been documented by more than fifty years of clinical use of specific metabolic inhibitors – methotrexate and nucleotides analogs. In this review we discuss one-carbon metabolism and nucleotide biosynthesis as common and specific features of many, if not all, tumors. The key enzymes involved in these pathways also represent promising anti-cancer therapeutic targets. We review different aspects of these metabolic pathways including their biochemistry, compartmentalization and expression of the key enzymes and their regulation at different levels. We also discuss the effects of known inhibitors of these pathways as well as the recent data on other enzymes of the same pathways as perspective pharmacological targets.
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