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. Author manuscript; available in PMC: 2021 Dec 30.
Published in final edited form as: Precis Cancer Med. 2021 Dec 30;4:38. doi: 10.21037/pcm-21-17

Figure 1.

Figure 1

Depiction of fluoropyrimidine metabolism and genetic factors influencing fluoropyrimidine toxicity. In most cancer patients >80% of 5-FU is degraded in the liver. However, for patients with certain DPYD polymorphisms reduced catabolism is accompanied by increased anabolic metabolism that perturbs RNA-mediated processes, particularly in the GI-tract and bone marrow, causing serious systemic toxicities. Several factors other than DPYD polymorphisms affect 5-FU toxicity including polymorphisms in miR-27a, polymorphisms in TYMS, an enzymatic target of 5-FU and levels of ENOSF1, a regulator of TYMS. p53 also regulates DPYD expression. The fluoropyrimidine polymer CF10 is directly converted to FdUMP and may circumvent issues related to genetic factors affecting 5-FU toxicity.