An Overview of CDK Enzyme Inhibitors in Cancer Therapy

Abstract: The ability to address the cell cycle in cancer therapy brings up new medication development possibilities. Cyclin-dependent kinases are a group of proteins that control the progression of the cell cycle. The CDK/cyclin complexes are activated when specific CDK sites are phosphorylated. Because of their non-selectivity and severe toxicity, most first-generation CDK inhibitors (also known as pan-CDK inhibitors) have not been authorized for clinical usage. Despite this, significant progress has been made in allowing pan-CDK inhibitors to be employed in clinical settings. Pan-CDK inhibitors' toxicity and side effects have been lowered in recent years because of the introduction of combination therapy techniques. As a result of this, pan-CDK inhibitors have regained a lot of clinical potential as a combination therapy approach. The CDK family members have been introduced in this overview, and their important roles in cell cycle control have been discussed. Then, we have described the current state of CDK inhibitor research, with a focus on inhibitors other than CDK4/6. We have mentioned first-generation pan-CDKIs, flavopiridol and roscovitine, as well as second-generation CDKIs, dinaciclib, P276-00, AT7519, TG02, roniciclib, and RGB-286638, based on their research phases, clinical trials, and cancer targeting. CDKIs are CDK4/6, CDK7, CDK9, and CDK12 inhibitors. Finally, we have looked into the efficacy of CDK inhibitors and PD1/PDL1 antibodies when used together, which could lead to the development of a viable cancer treatment strategy