Repurposed Anti-Cholesterol Drug Statin Can Stymie Cancer, Help Support Treatment, Say Researchers

Statins, which help treat high cholesterol, have been found to slow down the growth of colorectal tumours, according to a new study, making researchers consider the possibility of repurposing the drug to support cancer treatment.

However, more clinical trials are needed to provide scientific evidence before statins can become part of standard cancer treatment, they said.

Drug repurposing, an alternative to the conventional way of developing medicines from scratch, accelerates the pace of discovery since existing medicines and compounds being used for it have already passed safety tests.

Owing to a need to reduce the cost of developing drugs, the idea has gained traction in recent years with advances in computing power, artificial intelligence and bioinformatics helping in the identification of new uses for existing drugs more systematically and quickly.

Cancer is among the multiple diseases, including rheumatoid arthritis and HIV/AIDS, for which drug repurposing is being considered.

Senior author of the study, Sanjeev Galande, the dean of the School of Natural Sciences at Shiv Nadar University, said, 'Statins are known to lower cholesterol, and cholesterol metabolism is involved in colorectal cancer.' 'While certain cancers have shown signs of slowing down due to the use of statins, the precise and specific mode of action of the drugs has not been demonstrated yet,' he told PTI.

Galande's team, which included researchers from the Indian Institute of Science Education and Research (IISER), Pune, demonstrated through cell culture and experiments in mice how statins can arrest cancer growth at the molecular level and support treatment.

The findings have been published in the journal Oncotarget.

Colorectal cancer cells grown in the lab were treated with statins and found to display tumour-suppressing behaviour. 'Our findings strongly suggest that statins effectively mitigate the progression of colorectal tumour both in cultured (colorectal cancer) cells and in mice,' the study stated.

Galande and his team further found that molecules of the statin drug specifically targeted the 'Wnt/β-catenin' signalling pathway -- a series of interactions between molecules. Studies have shown this to be crucial to the formation of colorectal cancer adenoma -- a benign tumour originating in tissues lining organs and glands.

Specifically, statins were seen to reduce the action of the protein SATB1, which promotes tumour growth, and increase that of SATB2, which suppresses tumour growth. Both proteins act by regulating gene behaviour.

The change in gene activity arrested the growth of cancer cells in laboratory models that closely mimic the tumour, Galande explained.

'Overall, our findings suggest that statins hold the promise as a potential treatment for colorectal cancer and merit consideration for drug repurposing.

'While statins alone may not be sufficient as standalone cancer treatments given the limited clinical evidence, both preclinical and clinical studies indicate that combining statins with other therapies targeting diverse molecular pathways can significantly enhance their effectiveness,' he said.

Rituraj Purohit, senior principal scientist with the Council of Scientific and Industrial Research (CSIR)-Institute of Himalayan Bioresource Technology, Palampur, Himachal Pradesh, said that repurposed drugs can target secondary pathways, enhance tumour sensitivity, or modulate the tumour microenvironment, thereby improving treatment outcomes when used alongside standard therapies.

Standard treatments in cancer can involve surgery, chemotherapy (drugs) and radiation therapy.

Purohit, who is not involved with the study, opined that repurposed drugs, being widely available and affordable, can improve one's access to advanced cancer care, 'especially in resource-limited settings like India'.

He said the findings of the study on statins are 'promising' and 'provide evidence supporting further evaluation of statins in combination therapies'.

However, a 'majority of the study's data appear to be preclinical; and in vitro and in vivo results may not directly translate to human cancers', he said, adding the study looked at a small sample size.

Purohit is the co-author of a 2023 editorial, published in the journal Scientific Reports, which advocates for expanding the scope of repositioned drugs to COVID-19 and Alzheimer's disease, among others. However, challenges remain on the path to successful drug repurposing, including issues of selectivity and toxicity, the article says.

'Diseases like cancer and Alzheimer's are highly heterogeneous. A drug's efficacy in one subtype may not translate to another due to differences in molecular pathways, (tumour) microenvironments, or disease stages,' Purohit said.

He highlighted that the dosage of repositioned drugs may need to be varied to achieve efficacy, potentially resulting in unforeseen toxicity or reduced tolerability.

'Therefore, despite prior approval, demonstrating a repurposed drug's safety and efficacy in a new indication demands rigorous clinical trials. For diseases like Alzheimer's, the failure rate in late-stage trials remains particularly high,' Purohit added.

About the positioning of statins in cancer therapy, Galande stressed that well-structured clinical trials are needed to address uncertainties, including the ideal treatment regimen, tumour types most responsive to statins and which specific statins are most effective.