RNA May Boost Mesothelioma Chemotherapy Efficacy

Scientists tinkering with a specialized type of RNA molecule have found it may be possible to use the biologic building block to increase the effectiveness of mesothelioma chemotherapy.

The RNA molecule undergoing investigation is a nonviral antithymidylate synthase RNAi embedded liposome. RNAi means it’s an RNA molecule modified to interfere with biological processes.

In lab tests, researchers from Japan’s Tokushima University and Kyoto University found that antithymidylate synthase RNAi embedded liposome (TS shRNA lipoplex) could control a particular function of thymidylate synthase in malignant mesothelioma cells from the MSTO-211H line.

That matters because the function the scientists were able to control has a lot to do with a mesothelioma cell’s ability to withstand chemotherapy.

Basically, the TS shRNA lipoplex interfered with that function to such an extent that mesothelioma cell growth after chemotherapy was reduced considerably.

As a result, the lab mice used in testing the TS shRNA lipoplex experienced longer survival than would have been expected had they been given chemotherapy alone.

Mesothelioma Requires RNA

It must be emphasized that these promising results are simply that — promising. There is still a great deal more testing ahead to determine whether TS shRNA lipoplex is going to work the same in humans.

RNA is one of the two foundational nucleic acids found in mesothelioma and all other living cells. The other nucleic acid — the one with which you’re probably more familiar — is DNA.

RNA stands for ribonucleic acid. It is a polymeric molecule that contains at least one nucleotide. This nucleotide consists of a base, a ribose sugar and a phosphate. The base is made up of adenine, cytosine, guanine and uracil.

One of the functions of RNA is to transfer genetic information from a parent cell to an offspring cell. DNA does that too. But RNA handles a different aspect of the transfer.

RNA is also structured in a way that’s different from DNA. The biggest difference is that RNA’s ribose sugar contains a hydroxyl ingredient absent from the DNA version.

Lab-made RNA interference molecules are not new. They’ve been around for a while. But what is new is this use as a potential means of increasing the effectiveness of a mesothelioma treatment.

The Japanese scientists were attracted to RNAi as something worth investigating because of the molecules’ growing reputation for inhibiting tumor growth.

What they knew was that RNAi molecules do a very good job of blocking the expression of thymidylate synthase.

But there’s a problem with RNAi molecules in general. They tend to fall apart when you try to put them to work in a lab dish.

The Japanese scientists figured out a way to overcome this tendency so that they could deliver RNAi molecules to the targeted sites and get the job done.

Specialized RNA Molecule May Be Very Effective Against Mesothelioma

The scientists note that they tested TS shRNA lipoplex in conjunction with pemetrexed — the main ingredient that is considered part of the gold standard for mesothelioma chemotherapy.

“Our findings emphasize the pivotal relevance of RNAi as an effective tool for increasing the therapeutic efficacy of pemetrexed-based chemotherapy,” the scientists wrote in a recent issue of International Journal of Oncology.

They indicated this raises the possibility for the development of a novel therapeutic strategy.

If so, it may turn out to “surpass many of the currently applied, but less effective, therapeutic regimens against lethal malignant pleural mesothelioma,” they wrote.

Their article is “Downregulation of Thymidylate Synthase by RNAi Molecules Enhances the Antitumor Effect of Pemetrexed in an Orthotopic Malignant Mesothelioma Xenograft Mouse Model.”