Mesothelioma Commercial Cell Lines Alone Not Suitable for Early Testing of New Drugs, Study Reports

Mesothelioma Commercial Cell Lines Alone Not Suitable for Early Testing of New Drugs, Study Reports

Researchers at the University of Leicester, U.K., investigated whether mesothelioma tumor cells grown in a dish are truly similar to the cells found in the human cancer, work important to the preclinical testing of drugs to be evaluated in people. Their report, Molecular profiling reveals primary mesothelioma cell lines recapitulate human disease, which appeared on Feb. 19, 2016, in the journal Cell Death & Differentiation, found inadequacies in existing in vitro mesothelioma cell lines.

Mesothelioma refers to a malignant tumor in the lining of organs such as the lungs, stomach, and heart. Pleural mesothelioma, an aggressive cancer, is the most common form of the disease, amounting to 75 percent of all mesotheliomas. Its main cause is asbestos exposure, and its one-year survival rate is only 38 percent. Based on this low rate of survival, additional treatments are greatly needed. New research tools, such as cultured cells, can help scientists uncover possible mesothelioma treatments.

Several types of mesothelioma-like cultured cells are commercially available, but a detailed comparison of these commercial lines with patient-derived primary tumor cells to validate their suitability has been lacking.

The investigators, led by Tatyana Chernova of the MRC Toxicology Unit at Leicester, wanted to identify which of eight available cells lines might be the most accurate for the testing of medications under development for mesothelioma. The team analyzed several known biological markers that are commonly found in mesothelioma tumor cells, including a cellular marker called p53, and the tumor suppressor genes CDKN2A and NF2.

Overall, the researchers found that primary cells taken from patients were more likely to represent the disease than “cell lines,” which are purchased cells that have already divided multiple times, and are commonly used in research. The team furthermore discovered than no one cell type is best for studying mesothelioma, but that different cells and cell lines should be evaluated in order to test cells with multiple mesothelioma-specific markers.

Based on the results, they concluded, “Our results highlight that multiple, appropriately characterised, patient-derived tumor cell lines are required to enable concurrent evaluation of molecular profiles versus drug response. Furthermore, application of this approach to other difficult-to-treat tumors would generate improved cellular models for pre-clinical evaluation of novel targeted therapies.”

The research suggests that, ideally, medications for mesothelioma should be tested in several different cell types with the appropriate biological markers, and that initial drug screening should include tumor cells that have been directly taken from mesothelioma patients.

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