What Role Do Statins Play in Ovarian Cancer Treatment?
Pitavastatin may serve as a potential treatment for drug-resistant ovarian cancer.
Statins could eventually be an effective treatment against ovarian cancer, a new study suggests.
Although prior preclinical and retrospective studies suggest that statins could be a useful option to treat cancer—–to date, most statins have yet to demonstrate significant efficacy, except for one.
Scientists believe the statin pitavastatin could serve as a potential treatment candidate. Studies have shown that the physicochemical and pharmacological profile of pitavastatin suggests it may be the most likely statin to be efficacious in oncology clinical trials.
In a study published in Scientific Reports, investigators sought to justify clinical trials of pitavastatin in ovarian cancer by evaluating the drug’s activity against a panel of ovarian cancer cell lines.
“We believe we have found the answer to the paradox: for statins to be effective as a cancer therapy, the right statin needs to be used, it needs to be delivered at the right dose and interval, and diet needs to be controlled to reduce sources of geranylgeraniol, which can limit the statin’s effect on cancer cells,” the authors wrote.
Pitavastatin is unique in that it combines a suitably long metabolic half-life with a structure that allows it to continually inhibit tumor growth, indicating its potential usefulness in targeting ovarian cancer cells.
Xenograft studies in mice have shown pitavastatin’s ability to inhibit the growth of glioblastoma, further backing the theory. However, investigators for the first time reported that restriction of diet to eliminate geranylgeraniol allows statins to induce tumor regression.
“Pitavastatin was effective in all of the cell lines tested, with potencies differing by approximately 10-fold between different cell lines,” the authors wrote. “This may reflect a fundamental role of the mevalonate pathway in ovarian cancer cell biology.”
The investigators observed that the increased expression of wild-type and gain-of-function variants of TP53 resulted in an increase in HMGCR expression.
“Together with the wide spread dysregulation of TP53 in ovarian cancer, and the detection of HMGCR in a large proportion of ovarian cancer tumors, this suggests that a significant proportion of ovarian cancer patients may be candidates for treatment with pitavastatin,” the authors wrote.
The authors noted that pitavastatin retained its activity in matched cells obtained from patients both before and after the onset of drug resistance, suggesting the usefulness of statins to treat patients with chemotherapy-resistant cancer.
Currently, the investigators are in the planning stages to conduct full human clinical trials.
“The key message of our work is that clinical trials of pitavastatin can now be properly designed, and we are in the very early stages of developing trials without colleagues at Keele University and Birmingham University,” said co-author Dr Alan Richardson. “It is also noteworthy that pitavastatin is available in generic form, potentially making this a relatively inexpensive treatment.”