Yondelis (trabectedin), a drug derived from the Caribbean Sea cucumber, has shown promise for treating malignant pleural mesothelioma (MPM), according to a new study published in Molecular Cancer Therapeutics, the journal of the American Association for Cancer Research (AACR).
The study, “Trabectedin Is Active Against Malignant Pleural Mesothelioma Cell And Xenograft Models And Synergizes With Chemotherapy And Bcl-2 Inhibition In Vitro,” was conducted by researchers at the Comprehensive Cancer Center of MedUni Vienna and Vienna General Hospital in Austria.
Although MPM is considered a rare cancer, its incidence rate is rising. Associated with asbestos exposure, the disease is frequently treated with a combination of chemotherapy, surgery, and radiotherapy. But its tumors often develop resistance to treatment and lead to poor prognosis.
Yondelis is a chemotherapy already shown to be effective for treating other cancers such as malignant soft tissue tumors and ovarian cancer, with minimal impact on healthy pleural cells. The drug is also shown to contribute to the effects of Platinol (cisplatin) in certain cancers.
Current researchers showed that Yondelis is effective against mesothelioma in cultured cells and in animals. To develop other potential combination therapies with Yondelis, the team examined the gene signature of cell lines that were sensitive to Yondelis and compared it to those in cell cultures that were less sensitive to the treatment.
“Using bioinformatics, we were able to show that the increased formation of the protein bcl-2, which prevents cell death, reduces the effectiveness of [Yondelis],” Walter Berger, a senior c0-author of the study, said in a news release. The observation led the team to treat MPM cells with both Yondelis and the bcl-2 inhibitors Venclexta (venetoclax) and obatoclax.
“When [Yondelis] is combined with these bcl-2 inhibitors, there is a significant improvement in the destruction of malignant pleural mesothelioma cells,” said Alireza Hoda, the other senior co-author. “[Yondelis] therefore seems to be a new, effective and safe treatment option for this disease.”
The promising results were recently confirmed by interim results from the Phase 2 ATREUS clinical trial (NCT02194231) conducted in Italy.
“The study has even been met with great interest from people affected,” Berger said. “This is evidenced by the fact that the Comprehensive Cancer Centre publication has already been posted online and discussed in several international [forums] for asbestos and mesothelioma.”