CDK4/6 inhibitors as a novel therapeutic approach to treat estrogen receptor (ER) ‐positive breast cancer

Background and aim: One of the most common characteristics of various cancers is the cell cycle dysregulation. Impaired cyclin D-CDK4/6-Rb pathway has been frequently reported in the ER- positive breast cancers, typically associated with endocrine resistance. Among which the cyclin-dependent kinases (CDK) 4/6 inhibitors together with endocrine therapy have been useful in managing the ER+ metastatic breast cancer. The CDK4/6 is an important target in treating the types of cancer, especially in breast cancer, owing to effectively regulation of the cell cycle. Accordingly, one of the advancements in the therapeutic strategies against the breast oncology is oral highly selective CDK inhibitors, including palbociclib, ribociclib, and abemaciclib.Materials and methods: The present study was conducted by the search strategy on PubMed database in English using the keywords, including ER positive breast cancers, CDK4/6 inhibitors, resistance and therapeutic strategies.Results: The improved clinically treatment of hormone receptor-positive breast cancer has been recently reported by the small-molecule CDK4/6 inhibitors, promising success in other malignancies. The mentioned three anticancer drugs have attracted further attention owing to free survival progression on phase III trials and the most common side effects related to grade 3 treatment, including neutropenia, fatigue, nausea and diarrhea. There is no evidence on predictive biomarkers of response to CDK4/6 inhibitors, with the exception of estrogen receptor positivity. The mechanisms of achieving resistance to the CDK4 / 6 inhibitors appear to detect the CDK4/6 inhibitor-mediated therapeutic strategies.Conclusion: Based on the results, multi-omic methods are suggested to find a wide range of targets corresponding to cellular mechanisms for various applications in clinical purposes.

CDK4/6 inhibitors as a novel therapeutic approach to treat estrogen receptor (ER) ‐positive breast cancer Keywords:

ER positive breast cancers , CDK4/6 inhibitors , drug resistance , therapeutic strategies.