Targeting CDK1 in cancer: mechanisms and implications

Abstract

Cyclin dependent kinases (CDKs) are serine/threonine kinases that are proposed as promising candidate targets for cancer treatment. These proteins complexed with cyclins play a critical role in cell cycle progression. Most CDKs demonstrate substantially higher expression in cancer tissues compared with normal tissues and, according to the TCGA database, correlate with survival rate in multiple cancer types. Deregulation of CDK1 has been shown to be closely associated with tumorigenesis. CDK1 activation plays a critical role in a wide range of cancer types; and CDK1 phosphorylation of its many substrates greatly influences their function in tumorigenesis. Enrichment of CDK1 interacting proteins with Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was conducted to demonstrate that the associated proteins participate in multiple oncogenic pathways. This abundance of evidence clearly supports CDK1 as a promising target for cancer therapy. A number of small molecules targeting CDK1 or multiple CDKs have been developed and evaluated in preclinical studies. Notably, some of these small molecules have also been subjected to human clinical trials. This review evaluates the mechanisms and implications of targeting CDK1 in tumorigenesis and cancer therapy.

Investigating the effect of polymerase inhibitors on cellular proliferation: Computational studies, cytotoxicity, CDK1 inhibitory potential, and LC‐MS/MS cancer cell entrapment assays

“…Both DLT and RBV were found to be the frontier candidates based on their binding scores, especially towards the CDK1 target receptor (PDB ID:5HQ0); therefore, they were selected for further investigation. CDK1 is an integral and indispensable protein for cell cycle progression (Saito et al., 2016; Wang et al., 2023).…”

UBE2C is a diagnosis and therapeutic biomarker involved in immune infiltration of cancers including lung adenocarcinoma

“…CDK1 is unique among these CDKs as it plays a pivotal role in cell cycle progression by promoting G2/M phase transition and G1/S phase transition, and also G1 progression. Inhibition of CDK1 expression and activation effectively suppresses the function of many cancer cells [29]. The six conserved proteins (MCM2, MCM3, MCM4, MCM5, MCM6 and MCM7) form a hexameric complex as a DNA helicase, playing a crucial role in the initiation of DNA replication.…”

Do proton pump inhibitors affect the effectiveness of cyclin-dependent kinase 4/6 inhibitors in advanced HR positive, HER2 negative breast cancer? A meta-analysis

“…CDK 4/6 inhibitors within the CDK4 (INK4)-retinoblastoma (Rb) pathway govern the regulatory phases of the cell cycle, specifically orchestrating progression from G1 (pre-DNA synthesis) to S (DNA synthesis) ( Hamilton and Infante, 2016 ). CDK 4/6 assumes a pivotal role in overseeing the transition from G1 to S through its interaction with D-type cyclins, thereby inducing the phosphorylation of Rb ( Wang et al, 2023 ). Elevated cyclin-dependent kinase 4/6 activity ensues from mutations in CDK 4/6, the depletion of CDK regulators, and the heightened expression of D-type cycling—all converging to instigate the proliferation of cancer cells.…”