Document Type
Article
Publication Date
2025
Abstract
Given the pivotal role of CDK4/6 deregulation in the pathogenesis of various malignancies, CDK4/6 inhibitors have been incorporated into cancer treatment protocols. Beyond their antiproliferative effects, these inhibitors exhibit prominent immunomodulatory properties. Preclinical data indicated that CDK4/6 inhibitors enhance the tumor cell antigen presentation capacity and restrict the proliferation of immunosuppressive regulatory T-cells. Furthermore, studies showed that CDK4/6 inhibitors could enhance the development of memory T-cell in vivo in melanoma mouse models and in the clinical setting in breast cancer (BC) patients. In silico analysis identified 225 protein targets for CDK4/6 inhibitors involved in 57 immune-related pathways which further supported the immune-modulatory potential of these inhibitors in innate immunity, cytokine signaling, and adaptive immunity. Furthermore, 24 targets exhibited significantly higher protein expression in immune cell types compared to non-immune cell types, as indicated by data from the Human Protein Atlas. The favorable modulation of T-cell immunity by CDK4/6 inhibitors could complement the antitumor effect of immunotherapies, such as immune checkpoint inhibitors (ICIs), which hamper PD-1 /PD-L1 signaling and result in the reactivation of the antitumor T-cell response. Herein, we explore the clinical portfolio of CDK4/6 inhibitors across various solid malignancies, with emphasis on emerging combinations with ICIs.
Recommended Citation
Abdollah, Maha R.A.; Hussein, Sara A.; Saadawy, Ahmed H.; Badr, Eman; Wael, Neamtullah; Allam, Rasha M.; Al‑Abd, Ahmed M.; Sanchez, Ana Maria Roncero; and Tolba, Mai, "The landscape of cyclin‑dependent kinase 4/6 inhibitors in solid malignancies: emphasis on immunotherapy combinatorial strategies" (2025). Pharmacy. 881.
https://buescholar.bue.edu.eg/pharmacy/881