Renal Cancer Drug Temsirolimus Looks Promising for Mesothelioma

Temsirolimus is a mesothelioma drug you may not have heard of before. Chances are, however, you’ll be hearing quite a bit about it in the future.

One reason you may not have heard about it is that it’s not a mesothelioma drug. Not yet, not officially.

However, temsirolimus appears to be very good at causing mesothelioma cells to shut down and die, according to one recent study by Greek and British researchers, published in the journal Respirology.

After two or three weeks of testing temsirolimus against mesothelioma cells in the lab, growth of the cells was curtailed.

This occurred because the drug induced the cells to perform apoptosis. It also occurred because the drug inhibited tumor angiogenesis.

The drug also encouraged tumor lymphocytes to increase in number. Additionally, it hindered the mesothelioma cells’ attempts to corrupt friendly myeloid cells.

On top of all that, temsirolimus applied the brakes to NF-kappaB activation and kept immune-system macrophages from ignoring the presence of mesothelioma.

Temsirolimus Is a Surprising Choice for Mesothelioma

Temsirolimus is an inhibitor of the mechanistic target of rapamycin. The scientific shorthand for mechanistic target of rapamycin is mTOR.

The mTOR is bad because it picks up and carries signals that tell healthy cells to turn cancerous. It’s also bad because once the cells convert into cancer, mTOR encourages them to grow.

Temsirolimus is both a derivative and pro-drug of sirolimus. The U.S. Food and Drug Administration and the European Medicines Agency each approved temsirolimus in 2007. It was developed by Wyeth Pharmaceuticals. The brand name is Torisel.

Temsirolimus was a surprising choice of drug for the researchers to have settled upon. Its approved use is for treatment of renal cell carcinoma, not mesothelioma.

Still, the researchers — from Evangelismos Hospital in Athens and Churchill Hospital in Oxford — recognized the potential of temsirolimus for mesothelioma.

No humans were treated with the drug. Instead the researchers worked with lab cultures and mice.

Each mouse in the study was injected with cultivated mesothelioma cells. The mouse then received a 20 mg dose of temsirolimus five times per week for either 15 or 26 days, depending of which of two mesothelioma cell lines they received.

“We hypothesized that temsirolimus would curtail experimental mesothelioma progression in vivo by limiting tumor cell growth, abrogating tumor angiogenesis and modulating immune-inflammatory tumor milieu,” the researchers wrote.

Temsirolimus Tested in Lung Cancer, not Mesothelioma

For the most part, their hypothesis was borne out by the test results. Their work with temsirolimus followed research by another team of investigators that also studied the drug, only on non-small cell lung cancer.

That research, presented in Madrid at the 2014 European Society for Medical Oncology meeting, focused on temsirolimus’ ability to inhibit human epidermal growth factor receptor 2 — HER2.

Those researchers felt that HER2 mutations in non-small cell lung cancer made good treatment targets. They appear to have been correct.

At the end of a randomized, two-stage study of 27 patients with HER2-positive advanced, metastatic non-small cell lung cancer, 15 mg per week of intravenous temsirolimus was combined with neratinib. This resulted in an overall response rate of 21 percent in 14 of the patients.

The median progression-free survival was 4 months. But bear in mind that was not a test of temsirolimus against mesothelioma, but against non-small cell lung cancer.