One-carbon metabolism and nucleotide biosynthesis as attractive targets for anticancer therapy.
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.
Institute of Cytology RAS, Saint-Petersburg, Russian Federation.
Oleg
O
Shuvalov
Institute of Cytology RAS, Saint-Petersburg, Russian Federation.|Institute of Hematology, Almazov Federal North-West Medical Research Centre, Saint-Petersburg, Russian Federation.
Alexey
A
Petukhov
Institute of Cytology RAS, Saint-Petersburg, Russian Federation.
Alexandra
A
Daks
Institute of Cytology RAS, Saint-Petersburg, Russian Federation.
Olga
O
Fedorova
Institute of Cytology RAS, Saint-Petersburg, Russian Federation.
Elena
E
Vasileva
Institute of Cytology RAS, Saint-Petersburg, Russian Federation.
Nickolai A
NA
Barlev
D000818:Animals; D002244:Carbon / Q000378:metabolism*; D006801:Humans; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000628:therapy*; D009711:Nucleotides / Q000096:biosynthesis*
D009711:Nucleotides; D002244:Carbon
anti-cancer therapy; c-Myc; cancer metabolism; one-carbon metabolism; p53