# Cancer therapy by cyclin-dependent kinase inhibitors (CDKIs): bench to bedside

## TL;DR

This paper reviews how CDK inhibitors, which block cell division, are being developed and used to treat breast cancer and other cancers.

## Contribution

The paper provides a comprehensive review of CDK inhibitors, their mechanisms, and recent advancements in their clinical application.

## Key findings

- CDK4/6 inhibitors are FDA-approved for treating metastatic hormone receptor-positive breast cancer.
- Pan-CDK inhibitors face clinical challenges due to toxicity but show renewed promise in combination therapies.
- Recent combination therapy strategies have reduced the side effects of pan-CDK inhibitors.

## Abstract

A major characteristic of cancer is dysregulated cell division, which results in aberrant growth of cells. Consequently, medicinal targets that prevent cell division would be useful in the fight against cancer. The primary regulator of proliferation is a complex consisting of cyclin and cyclin-dependent kinases (CDKs). The FDA has granted approval for CDK inhibitors (CDKIs) to treat metastatic hormone receptor-positive breast cancer. Specifically, CDK4/6 CDKIs block the enzyme activity of CDK4 and CDK6. Unfortunately, the majority of first-generation CDK inhibitors, also known as pan-CDK inhibitors because they target multiple CDKs, have not been authorized for clinical use owing to their serious side effects and lack of selection. In contrast to this, significant advancements have been created to permit the use of pan-CDK inhibitors in therapeutic settings. Notably, the toxicity and negative consequences of pan-CDK inhibitors have been lessened in recent years thanks to the emergence of combination therapy tactics. Therefore, pan-CDK inhibitors have renewed promise for clinical use when used in a combination regimen. The members of the CDK family have been reviewed and their primary roles in cell cycle regulation were covered in this review. Next, we provided an overview of the state of studies on CDK inhibitors.