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.