Repurposed Statins in Cancer: Innovations, Mechanisms, Combination Therapies and Nanotechnology

Cholesterol-lowering statins act as repurposed drugs to enhance chemosensitivity, reduce chemotoxic, chemostatic, chemoresistance effects and radiation-toxicity. Statin drugs combined with concurrent chemotherapy and/or radiotherapy, initially target lipid metabolism to trigger pro-apoptosis, autophagy, antiproliferative, antiangiogenesis, immunosuppressant, anti-oxidant, cell cycle growth, control points, tumor microenvironment to reduce drug-resistance and delay the cancer progress to metastases in tumor cells. The clinical use of statin-chemoradiotherapy combinations in optimal doses is a new approach. Still dose-response and enhanced outcomes of statins are in infancy. It needs investigations on statin-statin, statin-chemo-radiotherapy, statin-immunosuppressor drug interactions, chemo-radiation dosage optimizations with patient safety. In available clinical trials, a subgroup analysis on prospective vs retrospective study design showed altered mechanisms of statin actions on cancer pathways and indicated the combined therapy benefits. The present study presents the concepts of statin-responsive cancer classification, a proposed criteria and prescription of statins combined with chemo-radiotherapy to target tumors, drug-drug interactions in cancer theranosis, cancer prediction and patient outcomes based on reported clinical trials. The optoimized statins combined with chemotherapy with radiotherapy may reduce the toxicity and chemoresistance to enhance patient and clinical outcomes