Abstract
Cell cycle deregulation is a characteristic feature of malignant tumours. Research in cell cycle control made it possible to identify potential treatment targets of anti-tumour therapy.
Palbociclib is a selective inhibitor of cyclin-dependent kinases 4/6 (CDK4/6) that regulates the transition of cells from G1 to S phase. Inhibition of this step stops the cell cycle and also tumour progression through the inclusion of retinoblastoma protein (Rb) and the family of E2F transcription factors.
The blockade is most successful in HER2-negative HR-positive malignant tumours. Based on the results of randomized clinical trials palbociclib has been accorded accelerated FDA approval for its combination with letrozole in first-line therapy of metastatic hormone-dependent HER2-negative breast cancer, and later also together with fulvestrant in the therapy of metastatic hormone-dependent HER2-negative breast cancer after endocrine therapy failure.