Universität zu Köln

Robinson, Alyncia D., Eich, Marie-Lisa and Varambally, Sooryanarayana (2020). Dysregulation of de novo nucleotide biosynthetic pathway enzymes in cancer and targeting opportunities. Cancer Lett., 470. S. 134 - 141. CLARE: ELSEVIER IRELAND LTD. ISSN 1872-7980

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Abstract

Cancer is a disease of uncontrolled cell growth and a major cause of death worldwide. Many molecular events characterize tumor initiation and progression. Global gene expression analyses using next-generation sequencing, proteomics and metabolomics show genomic, epigenetic, and metabolite concentration changes in various tumors. Molecular alterations identified include multiple cancer-driving mutations, gene fusions, amplifications, deletions, and post-translational modifications. Data integration from many high-throughput platforms unraveled dysregulation in many metabolic pathways in cancer. Since cancer cells are fast-growing, their metabolic needs are enhanced, hence the requirement for de novo synthesis of essential metabolites. One critical requirement of fast-growing cells and a historically important pathway in cancer is the nucleotide biosynthetic pathway and its enzymes are valuable targets for small molecule inhibition. Purines and pyrimidines are building blocks of DNA synthesis and due to their excessive growth, cancer cells extensively utilize de novo pathways for nucleotide biosynthesis. Methotrexate, one of the early chemotherapeutic agents, targets dihydrofolate reductase of the folate metabolic pathway that is involved in nucleotide biosynthesis. In this review, we discuss the nucleotide biosynthetic pathways in cancer and targeting opportunities.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Robinson, Alyncia D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Eich, Marie-Lisa UNSPECIFIED UNSPECIFIED UNSPECIFIED Varambally, Sooryanarayana UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-351624
DOI:	10.1016/j.canlet.2019.11.013
Journal or Publication Title:	Cancer Lett.
Volume:	470
Page Range:	S. 134 - 141
Date:	2020
Publisher:	ELSEVIER IRELAND LTD
Place of Publication:	CLARE
ISSN:	1872-7980
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ONE-CARBON METABOLISM; RIBONUCLEOTIDE TRANSFORMYLASE; CRYSTAL-STRUCTURE; BREQUINAR SODIUM; GENE-EXPRESSION; C-MYC; INHIBITORS; MECHANISMS; SERINE; POTENT Multiple languages Oncology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/35162