Compound Makes Mesothelioma Tumors More Susceptible to Chemo

Swiss cancer researchers may have found a way to get around malignant mesothelioma’s notorious resistance to chemotherapy with an investigational metal-based compound called RAPTA-T.

Malignant pleural mesothelioma is an incurable and highly aggressive cancer. One of the reasons it is so deadly is that it rarely responds to standard cancer treatments. Even the treatment combination that is considered the standard of care for pleural mesothelioma—pemetrexed (Alimta) and cisplatin—is only effective in about 4 out of 10 patients.

But scientists with Centre Hospitalier Universitaire Vaudois and the Swiss Federal Institute of Technology in Lausanne, Switzerland have discovered a counterintuitive way to ramp up the cancer-killing power of mesothelioma chemotherapy.

Creating a “Healthier” Tumor

The element on which the RAPTA-T compound is based is ruthenium, a transition metal belonging to the platinum group on the periodic table.

In a new article in the journal Scientific Reports, the team explains how they used RAPTA-T to increase the uptake of chemotherapy drugs in a mouse model of human malignant mesothelioma.

According to the report, when RAPTA-T was given to mice that had been implanted with human mesothelioma tumors, it enhanced the vascularization of the tumors, improving blood flow and increasing oxygenation.

When the treated “healthier” tumors were then given chemotherapy with cisplatin, they were primed to absorb more of the toxin which, in turn, slowed their growth.

“RAPTA-T pre-treatment followed by the application of cisplatin…leads to increased levels of the cytotoxin in the tumor and enhanced mesothelioma growth inhibition,” writes first author Tina Riedel of the Swiss Federal Institute of Technology. “These findings suggest novel therapeutic implications for RAPTA-T to create conditions for superior drug uptake and efficacy…in malignant pleural mesothelioma…”

While RAPTA-T is chemically similar to cisplatin, it is still undergoing preclinical evaluation and is not an approved cancer drug. Some studies of RAPTA-T and other ruthenium anticancer compounds have suggested that they may be an alternative to cisplatin with fewer side-effects.

Chemotherapy for Pleural Mesothelioma

Most patients who are diagnosed with pleural mesothelioma will have chemotherapy with cisplatin and Alimta, the only drug approved specifically for the treatment of malignant mesothelioma.

Because this combination produces dose-limiting side effects, it is usually combined with other cancer treatments which may include surgery, radiation, or immunotherapy.

Multiple studies have found that the patients who experience the best outcomes and the longest mesothelioma survival are those who receive several different kinds of treatments.

Source:

Riedel, T, et al, “Chemo-manipulation of tumor blood vessels by a metal-based anticancer complex enhances antitumor therapy”, Juy 6, 2018, Scientific Reports