Statins, Antihypercholesterolemic Drugs Show Potential as Anticancer Agents

Statins could be used in combination with anticancer drugs, possibly adding a clinical benefit, according to researchers in Greece. They report that hypercholesterolemia and tumorigenesis are interrelated and studies are now warranted to investigate whether some statins should be part of combination or triple therapy in some tumor types. Writing in OncoTargets and Therapy, they argue that in vitro, in vivo, and clinical data now support a potential role for certain cholesterol-lowering drugs in treating a variety of cancers.^[1]

Panagiota Papanagnou, from Agios Savvas Cancer Hospital, Athens, Greece, and colleagues conducted a review of the antitumor activity of widely prescribed marketed antihypercholesterolemic drugs, statins, and ezetimibe. They report that bile acid sequestrants (cholestyramine, colestipol, and colesevelam) currently show no evidence of anticancer activity.

The research team found that ezetimibe’s function goes beyond NPC1L1 regulation to interfering with tumor microvascularization. They propose that different pathways may be involved and merit further research. Simvastatin may have the ability to help combat non-small cell lung cancer (NSCLC), breast cancer, and renal cell carcinoma (RCC), the investigators reported. In addition, clinical data suggested that clinically relevant doses of simvastatin (40 mg/day) combined with the conventional chemotherapeutic scheme of irinotecan with fluorouracil (5FU) and folinic acid (FOLFIRI) may benefit patients with metastatic colorectal cancer.

Lovastatin appears to have capabilities for combating melanoma and several other cancers, including medulloblastoma and mesothelioma. It has shown particularly promising activity against NSCLC and prostate cancer. Atorvastatin may help combat pancreatic cancer and colon adenocarcinomas, and fluvastatin may have antitumor activity against RCC and leukemia.

This current review examines the anticancer properties of drugs used in the management of hypercholesterolemia and points to a new way of viewing all marketed antihypercholesterolemic agents. Academic thoracic oncologist Jonathan Lehman, MD, PhD, an instructor in medicine in the division of hematology/oncology at Vanderbilt University Medical Center in Nashville, Tennessee, said the idea of repurposing these agents is attractive because they have established safety and dosing regimens. They are also already approved by the US Food and Drug Administration. 

“This means that if they are effective, they could enter clinic faster. Unfortunately, many compounds and drugs appear very promising in early research, but do not work in clinical trials, or work in early clinical trials, but not in larger ones. Others only work in specific situations with specific cancers,” Dr Lehman told Oncology Nurse Advisor.