Gene-Based Mesothelioma Treatment Could Improve Chemotherapy, According to Surviving Mesothelioma

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A team of international researchers say “turning off” the gene for mesothelin slows the spread of mesothelioma and sensitizes cells to cisplatin therapy.

MSLN-silencing caused decreased proliferation rate and reduced invasive capacity...

New research published in the online open-access medical journal PLoS One and reported by Surviving Mesothelioma suggests that “knocking down” mesothelin production with synthetic RNA may offer a novel approach to treating malignant pleural mesothelioma.

Mesothelioma is one of several cancers that overexpress the protein mesothelin. Although the relationship between mesothelin and malignancy is not fully understood, some scientists believe that mesothelin may play a role in the development and spread of mesothelioma and other cancers.

Mesothelin-silencing at the gene level has been tested in both ovarian and pancreatic cancers. To see how the method might work in the treatment of mesothelioma, researchers from Italy, the UK, and Japan measured the expression of mesothelin in three different mesothelioma cell lines and one non-mesothelioma control cell line. They then “knocked down” the expression of mesothelin by targeting the MSLN gene that encodes for the protein. By inserting synthetic silencing RNA (siRNA) into the MSLN gene, the researchers turned down mesothelin expression with promising results.

“In agreement with previous studies, transient MSLN-silencing caused decreased proliferation rate and reduced invasive capacity and sphere formation in MSLN-overexpressing Mero-14 cells [one of the mesothelioma cell lines],” they report. In addition, using siRNA to silence mesothelin expression also seemed to make mesothelioma cells more susceptible to the negative effects of cisplatin chemotherapy. Together, the two approaches worked better at slowing mesothelioma spread than either treatment alone.

The authors of the new study conclude that the MSLN gene “should be considered a key molecular target” for new types of gene-based therapies for mesothelioma. Novel therapeutic approaches like gene therapy are considered the best hope for fighting mesothelioma, since conventional treatments tend to have only limited effects.

The original study was published in PLoS One. (Melaiu, O, et al, “MSLN Gene Silencing has an Anti-Malignant Effect of Cell Lines Overexpressing Mesothelin Deriving from Malignant Pleural Mesothelioma”, January 21, 2014, PLoS One,

For nearly ten years, Surviving Mesothelioma has brought readers the most important and ground-breaking news on the causes, diagnosis and treatment of mesothelioma. All Surviving Mesothelioma news is gathered and reported directly from the peer-reviewed medical literature. Written for patients and their loved ones, Surviving Mesothelioma news helps families make more informed decisions.

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Michael Ellis
Cancer Monthy
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