4.6 Review

Targeting Pyrimidine Metabolism in the Era of Precision Cancer Medicine

Journal

FRONTIERS IN ONCOLOGY
Volume 11, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fonc.2021.684961

Keywords

metabolic reprogram; pyrimidine metabolism; precision medicine; dihydroorotate dehydrogenase; pyrimidine inhibitor

Categories

Funding

  1. National Natural Science Foundation of China [81973362, 81972828]
  2. Shanghai Committee of Science and Technology [18431900500, 19ZR1473500]
  3. Open Research Project of Key Laboratory of High-Incidence-Tumor Prevention & Treatment (Guangxi Medical University), Ministry of Education

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Metabolic rewiring is a primary feature of cancer, with nucleotide biosynthesis being closely linked to cancer progression. Drugs targeting pyrimidine metabolism have limitations in efficacy and side effects, prompting the need for better strategies to inhibit pyrimidine metabolism in cancer.
Metabolic rewiring is considered as a primary feature of cancer. Malignant cells reprogram metabolism pathway in response to various intrinsic and extrinsic drawback to fuel cell survival and growth. Among the complex metabolic pathways, pyrimidine biosynthesis is conserved in all living organism and is necessary to maintain cellular fundamental function (i.e. DNA and RNA biosynthesis). A wealth of evidence has demonstrated that dysfunction of pyrimidine metabolism is closely related to cancer progression and numerous drugs targeting pyrimidine metabolism have been approved for multiple types of cancer. However, the non-negligible side effects and limited efficacy warrants a better strategy for negating pyrimidine metabolism in cancer. In recent years, increased studies have evidenced the interplay of oncogenic signaling and pyrimidine synthesis in tumorigenesis. Here, we review the recent conceptual advances on pyrimidine metabolism, especially dihydroorotate dehydrogenase (DHODH), in the framework of precision oncology medicine and prospect how this would guide the development of new drug precisely targeting the pyrimidine metabolism in cancer.

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