Journal
CANCER & METABOLISM
Volume 8, Issue 1, Pages -Publisher
BMC
DOI: 10.1186/s40170-020-00218-5
Keywords
Pyrimidine ribonucleotide metabolism; Cancer therapy; CAD; DHODH; UMPS; Nucleoside transporters; CDA; CTPS; Therapeutic index
Categories
Funding
- Swedish Research Council
- Swedish Cancer Society
- Swedish Childhood Cancer Foundation
- Karolinska Institute
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By providing the necessary building blocks for nucleic acids and precursors for cell membrane synthesis, pyrimidine ribonucleotides are essential for cell growth and proliferation. Therefore, depleting pyrimidine ribonucleotide pools has long been considered as a strategy to reduce cancer cell growth. Here, we review the pharmacological approaches that have been employed to modulate pyrimidine ribonucleotide synthesis and degradation routes and discuss their potential use in cancer therapy. New developments in the treatment of myeloid malignancies with inhibitors of pyrimidine ribonucleotide synthesis justify revisiting the literature as well as discussing whether targeting this metabolic pathway can be effective and sufficiently selective for cancer cells to warrant an acceptable therapeutic index in patients.
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