Addressing delivery and resistance issues of CDK4/6 inhibitors as cancer therapeutics.

Cancer treatment is limited by poor specificity, efficacy, toxicity and resistance associated with conventional treatment options involving surgery, chemotherapy, and radiation therapy. The introduction of newer targeted agents, such as cyclin-dependent kinases-4 and -6 (CDK4/6) inhibitors, in the treatment of hormone receptor-positive breast cancer has improved breast cancer treatment. However, the high dose, frequent administration, and acquired resistance of these newer anti-cancer molecules significantly limits their therapeutic application. In this review, we explore the current landscape of nanoformulations and advanced formulation strategies, including lipid and polymeric-based systems, salt forms, and inclusion complexes, for improving the efficacy of CDK4/6 inhibitors and circumventing resistance mechanisms. Overall, these novel formulation strategies represent a promising frontier for improving the clinical potential of CDK4/6 inhibitor therapy.