Statins in Cancer Prevention and Therapy

SIMPLE SUMMARY: Retrospective studies of common malignancies such as head and neck cancer often report lower incidence and/or better outcomes for patients incidentally treated with statins, the HMG-CoA reductase inhibitors commonly prescribed to reduce blood cholesterol and related cardiovascular risks. Lipophilic statins have been proposed to both sensitize to therapy and spare normal tissue, suggesting particular benefits in head and neck cancer, where treatment often incurs major toxicities. While roles for statins in prevention remain controversial, rigorous laboratory studies have confirmed the direct effects of statins on cells and tumors that enhance response to chemotherapy, radiation, targeted agents and immunotherapy. This review surveys the literature on mechanisms of action and features of tumors that may mediate the benefits of statins during and following treatment for head and neck cancer. Statins may have their greatest impact on radiotherapy, suggesting prospective studies of prolonged treatment in selected patients toward the long-term goal of treatment de-intensification. ABSTRACT: Statins, a class of HMG-CoA reductase inhibitors best known for their cholesterol-reducing and cardiovascular protective activity, have also demonstrated promise in cancer prevention and treatment. This review focuses on their potential applications in head and neck cancer (HNC), a common malignancy for which established treatment often fails despite incurring debilitating adverse effects. Preclinical and clinical studies have suggested that statins may enhance HNC sensitivity to radiation and other conventional therapies while protecting normal tissue, but the underlying mechanisms remain poorly defined, likely involving both cholesterol-dependent and -independent effects on diverse cancer-related pathways. This review brings together recent discoveries concerning the anticancer activity of statins relevant to HNC, highlighting their anti-inflammatory activity and impacts on DNA-damage response. We also explore molecular targets and mechanisms and discuss the potential to integrate statins into conventional HNC treatment regimens to improve patient outcomes.