Diet May Be Reason Pitavastatin, a Statin, Failed to Arrest Ovarian Cancer in Clinical Trials, Study Says

Diet May Be Reason Pitavastatin, a Statin, Failed to Arrest Ovarian Cancer in Clinical Trials, Study Says

Pitavastatin, part of a class of statins widely used to lower blood cholesterol levels, was found to successfully target ovarian cancer cells and reduce tumor growth in mice, according to a recent report published in the journal Scientific Reports.

But the study, “Dietary geranylgeraniol can limit the activity of pitavastatin as a potential treatment for drug-resistant ovarian cancer,” suggests that certain dietary compounds, like geranylgeraniol that is found in sunflower oil and some rice, may halt the anti-tumor potential of this statin. The finding could be significant, because statins have long been seen as a possible anti-cancer agents but failed to show benefits in studies involving actual patients. This research points to diet as a likely reason, and new clinical trials are being planned.

Nearly 65 percent of ovarian cancers have high levels of hydroxymethylglutarate coenzyme-A reductase (HMGCR), a key enzyme involved in the synthesis of cholesterol. Because HMGCR contributes to the growth of cancer cells, researchers have hypothesized for a long time that targeting this enzyme could be a promising way to attack cancer — and its link to cholesterol led them to look at statins.

But while preclinical studies have suggested that statins, which block cholesterol synthesis, have the potential to target cancer cells, these compounds have failed to show beneficial results in human clinical trials.

Researchers at the Keele University in the U.K. had previously shown that this was due in part to the reduced stability and half-life of the statins used in the trials. Now, they found that a specific, more stable statin called pitavastatin can target HMGCR, and could be used against ovarian cancer cells.

The research team showed that pitavastatin, marketed in the U.S. under the brand name Livalo and in Europe as Livazo, could induce death in lab-grown ovarian cancer cells.

In ovarian cancer mice models, however, this statin failed to reduce tumor growth. These puzzling, contradictory results prompted the researchers to question whether dietary compounds could interfere with the activity of pitavastatin.

They found that a fat compound called geranylgeraniol, which can be found in rice and sunflower oil, was an inhibitor of pitavastatin. When the animal experiments were repeated with mice fed a controlled diet — one without any source of geranylgeraniol — pitavastatin was seen to significantly reduce tumor growth.

These results suggest that diet components can inhibit the anti-tumor activity of statins, and possibly help to explain previous failures of statin use in clinical trials.

“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,” Dr. Alan Richardson, senior co-author of the study, said in a news release.

Based on the therapeutic potential of pitavastatin on ovarian cancer cells, the research team and its collaborators have begun planning for clinical trials to again be conducted in patients.

“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 with our colleagues at Keele University and Birmingham University. It is also noteworthy that pitavastatin is available in a generic form, potentially making this a relatively inexpensive treatment,” said Richardson.

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