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New Approach Enhances Mesothelioma Survival in Mice on Chemo

1716415_mouseEven the best chemotherapy for malignant mesothelioma has limited effectiveness. But new research suggests that manipulating a mesothelioma patient’s RNA may offer a way to change that.

Most mesothelioma patients will undergo chemotherapy as part of their treatment.

Pemetrexed (Alimta) is the mainstay of mesothelioma treatment, even though a substantial percentage of mesothelioma patients don’t respond to it.

Now, a study conducted in Japan suggests that RNA interference technology (RNAi) can make mesothelioma cells more susceptible to chemotherapy and potentially improve mesothelioma survival.

RNA in Malignant Mesothelioma

Ribonucleic acid (RNA) is a molecule that acts as a messenger, carrying and translating instructions from DNA that control critical cellular processes, from metabolism to replication and death.

Cancer researchers have found that, by manipulating the RNA with specially designed molecules, they can enhance the effectiveness of certain chemotherapy agents.

In the current study, researchers at the Institute of Health Biosciences at Japan’s Tokushima University aimed to downregulate a particular enzyme (thymidylate synthase or TS) in malignant mesothelioma cells to make them more sensitive to pemetrexed.

Testing RNAi in Mesothelioma Treatment

To test their theory, the Japanese researchers first embedded new RNA into mesothelioma cells in the lab using a tiny bubble called a liposome.

The new “programming” enhanced the antitumor effects of the pemetrexed, inhibiting mesothelioma cell growth.

The results were equally encouraging in live mice with mesothelioma. When the mice got a combination of pemetrexed and the RNA-manipulating liposome, mesothelioma tumor progression slowed down and the mice survived longer than with pemetrexed alone.

The Future of Mesothelioma Therapy?

In a report of their findings in the International Journal of Oncology, the team expressed optimism for the future of mesothelioma treatment.

“Our findings emphasize the pivotal relevance of RNAi as an effective tool for increasing the therapeutic efficacy of pemetrexed, a cornerstone in the treatment regimens of malignant pleural mesothelioma,” writes lead author Amr S. Abu Lila.

Abu Lila and his colleagues say the study raises the possibility of a novel therapeutic strategy, combining the liposome they developed with pemetrexed to improve mesothelioma outcomes for human patients.


Abu Lila, AS, et al, Downregulation of thymidylate synthase by RNAi molecules enhances the antitumor effect of pemetrexed in an orthotopic malignant mesothelioma xenograft mouse model”, February 1, 2016, International Journal of Oncology, Epub ahead of print

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