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Autophagy Inhibitors Potentially Make Chemotherapy More Effective in Mesothelioma Patients

Published: November 15, 2017

Autophagy is a natural and regulated self-degradative process in cells that plays a critical role in balancing sources of energy and removing aggravated proteins, damaged organelles, and pathogens. During autophagy, cells break down and recycle their different parts in order to make new cells. In mesothelioma, autophagy is necessary for mesothelial cell growth.

A recent study published in Molecular Carcinogenesis, investigated autophagy and its effects on different stages of chemotherapy treatment of mesothelioma. Using 3-D models of pleural mesothelioma, scientists and researchers from the University of California and Harvard Medical School were able to determine that by blocking autophagy in mesothelioma patients, chemotherapy treatments may be more effective.

To inhibit autophagy, the 3-D models were either given an early stage ULK1/2 inhibitor (a protein kinase essential for the beginning phases of autophagy), or a later stage hydroxychloroquine inhibitor. Results showed that when autophagy was subdued at the early stage, the mesothelioma cells showed more sensitivity, which could result in chemotherapy treatments being more effective.

Malignant pleural mesothelioma has been proven difficult to treat. The aggressive cancer, once discovered, quickly spreads – allowing little time for traditional chemotherapy treatments to work. Surgery and immunotherapy treatments are also an option for anyone suffering from mesothelioma, but just like with chemotherapy, these treatments are found to be much more effective if the cancer is caught in its early stages. Unfortunately, due to the long latency period of the disease, and the fact the symptoms often mimic less serious conditions, mesothelioma is rarely caught in its early stages.

The inhibitors did not cause the cells to die completely, so the process of inhibiting autophagy is not miracle cure for those suffering from this aggressive cancer.  However, any process that has a positive effect on mesothelioma treatments gives hope to scientists and researchers that the cure for mesothelioma is still within reach.

Source:

Follo C., et. al., “Inhibition of autophagy initiation potentiates chemosensitivity in mesothelioma,” Molecular Carcinogenesis (October 27, 2017). [Link]

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