One-carbon metabolism and nucleotide biosynthesis as attractive targets for anticancer therapy
Year: 2017
Type: review
Abstract: // Oleg Shuvalov 1 , Alexey Petukhov 1, 2 , Alexandra Daks 1 , Olga Fedorova 1 , Elena Vasileva 1 , Nickolai A. Barlev 1 1 Institute of Cytology RAS, Saint-Petersburg, Russian Federation 2 Institute of Hematology, Almazov Federal North-West Medical Research Centre, Saint-Petersburg, Russian Federation Correspondence to: 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 ABSTRACT 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.
Source: Oncotarget
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: diamond
Awards: G1553259023, G4570164369
OpenAlex ID: W2585195223