The Emerging Role of Cdk5 in Cancer

Abstract

Cdk5 is an atypical cyclin-dependent kinase that is well characterized for its role in the central nervous system rather than in the cell cycle. However Cdk5 has been recently implicated in the development and progression of a variety of cancers including breast, lung, colon, pancreatic, melanoma, thyroid and brain tumors. This broad pro-tumorigenic role makes Cdk5 a promising drug target for the development of new cancer therapies. Here we review the contribution of Cdk5 to molecular mechanisms that confer upon tumors the ability to grow, proliferate and disseminate to secondary organs, as well as resistance to chemotherapies. We subsequently discuss existing and new strategies for targeting Cdk5 and its downstream mechanisms as anti-cancer treatments.

Proteomics, Post-translational Modifications, and Integrative Analyses Reveal Molecular Heterogeneity within Medulloblastoma Subgroups

“…It is overexpressed in many cancers (McCubrey et al, 2014) and its substrates have increased phosphorylation in the Group 4 and SHHb samples. CDK5 has been associated with oncogenesis and resistance to cancer therapies (Pozo and Bibb, 2016) and its targets had increased phosphorylation in Group 4. CDK5 phosphorylates MYC at S62, much like CDK1 and CDK7, which were fittingly associated with G3a.…”

Synthesis of aminopyrazole analogs and their evaluation as CDK inhibitors for cancer therapy

“…11 CDK5 is an atypical cyclin-dependent kinase, best known for its role in the central nervous system and regulates development, axon elongation, and neuronal migration. 12 Unlike other CDKs, which are activated by cyclins, CDK5 is activated by regulatory proteins p35 and p39. Recently, CDK5 was found to possess non-neuronal functions, which include apoptosis, senescence, angiogenesis, insulin secretion, wound healing, and adhesion/migration, many of which are the hallmarks of tumorigenesis and thus an attractive target for therapeutic intervention against cancer.…”

Selective Ablation of Tumor Suppressors in Parafollicular C Cells Elicits Medullary Thyroid Carcinoma

“…In fact, MTC accounts for more than 14% of thyroid cancer-related deaths. Uncovering new genes and pathways required for the development or survival of medullary thyroid carcinoma (7,8) is critical to inventing novel targeted therapies or other options for treating these patients (9,10).…”