CDKinhibiittoreiden

CDKinhibiittoreiden, commonly referred to as cyclin-dependent kinase inhibitors (CDK inhibitors), are a class of small-molecule drugs that block the activity of cyclin-dependent kinases. CDKs regulate cell cycle progression by phosphorylating substrates such as the retinoblastoma (RB) protein. Inhibitors can be selective for CDK4 and CDK6 or broadened to other CDKs. By preventing RB phosphorylation, these drugs often cause G1 cell-cycle arrest and reduced cellular proliferation; some settings also trigger apoptosis. Resistance can arise through loss of RB, upregulation of cyclin E, or activation of alternative signaling pathways.

Clinically, the most well-established CDK inhibitors are selective CDK4/CDK6 inhibitors, including palbociclib, ribociclib, and abemaciclib. They are approved for hormone receptor–positive, HER2-negative advanced breast cancer, typically in combination with endocrine therapy such as aromatase inhibitors or fulvestrant. Beyond breast cancer, CDK inhibitors are being explored in other solid tumors and hematologic malignancies, with varying degrees of success. Pan-CDK inhibitors, such as early agents flavopiridol and others, demonstrated antitumor activity but often encountered greater toxicity, limiting their broad use.

History and development of CDK inhibitors began with earlier compounds like roscovitine and flavopiridol in the 1990s. The CDK4/CDK6-selective inhibitors gained prominence with the approval of palbociclib in 2015, followed by ribociclib and abemaciclib. Current research topics include understanding resistance mechanisms, identifying predictive biomarkers (e.g., RB status, cyclin E amplification), and optimizing combination regimens to improve efficacy while managing hematologic and other toxicities.