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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调节嘧啶核糖核苷酸水平以治疗癌症

通过为核酸和细胞膜合成前体提供必要的结构单元，嘧啶核糖核苷酸对细胞生长和增殖至关重要。因此，耗尽嘧啶核糖核苷酸库长期以来一直被认为是减少癌细胞生长的策略。在这里，我们回顾了用于调节嘧啶核糖核苷酸合成和降解途径的药理学方法，并讨论了它们在癌症治疗中的潜在用途。使用嘧啶核糖核苷酸合成抑制剂治疗髓系恶性肿瘤的新进展证明重新审视文献以及讨论靶向该代谢途径是否对癌细胞有效且具有足够的选择性以保证患者可接受的治疗指数是合理的。