Targeting cyclin-dependent kinases in gastrointestinal cancer therapy.

Cyclin-dependent kinases (CDKs) play an important role in cell-cycle progression. CDKs are positively modulated by regulatory mitotic cyclins and negatively controlled by endogenous CDK inhibitors (CDKIs) cyclically as cells progress through different cell cycles of transitions. When activated by cyclins, cyclin-CDK complexes were able to facilitate the transition of cell cycle from one phase to the next, e.g., from G1 to S or from G2 to M. DNA damages may cause inhibition of CDKs leading to cell-cycle arrest, while unrepairable DNA damage causes cells to undergo apoptosis. Disruption of cell cycle progression is an important cancer hallmark to mediate uncontrolled cell proliferation, tumorigenesis, and metastasis. Aberrantly expressed CDKs are causally linked to the development of gastrointestinal cancers, and as such, CDKs may not only form a class of potential biomarkers for the diagnosis and therapy of gastrointestinal cancers. In this review article, we summarized the data from translational studies using CDKs as a target for gastrointestinal cancer treatment.