CDK46selektiivisiä

CDK46selektiivisiä refers to selective inhibitors of cyclin-dependent kinases 4 and 6 (CDK4 and CDK6). These kinases are critical regulators of the cell cycle, specifically promoting the transition from the G1 phase to the S phase. In many cancers, CDK4 and CDK6 are overactive, leading to uncontrolled cell proliferation.

Selective CDK46 inhibitors are a class of targeted therapy drugs designed to block the activity of these specific kinases. By inhibiting CDK4 and CDK6, these drugs prevent the phosphorylation of the retinoblastoma protein (Rb). Phosphorylation of Rb normally releases it from its inhibitory complex with E2F transcription factors, allowing for cell cycle progression and DNA replication. When Rb remains unphosphorylated due to CDK46 inhibition, the cell cycle is arrested in the G1 phase, thereby halting tumor growth.

These inhibitors have demonstrated significant efficacy, particularly in the treatment of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer. Clinical trials have shown that combining CDK46 inhibitors with endocrine therapy improves progression-free survival and overall survival compared to endocrine therapy alone.

Examples of approved CDK46 inhibitors include palbociclib, ribociclib, and abemaciclib. While generally well-tolerated, common side effects can include neutropenia, fatigue, nausea, and diarrhea, depending on the specific agent. Ongoing research is exploring the use of CDK46 inhibitors in other cancer types and in combination with various therapeutic strategies.