Pleural mesothelioma (PM): New therapeutic approach to chemo-and radiotherapy sensitivity enhancement by Medical University of Vienna

A recent research study led by Karin Schelch and Michael Grusch from MedUni Vienna identified the oncoprotein YB-1 as an attractive therapeutic target in PM and demonstrates that indirect targeting of YB-1 is a promising approach to enhance sensitivity to chemo- and radiotherapy. 

The pleura, a thin lining that covers the chest cavity and surrounds the lungs, is the primary target of the uncommon and severe malignancy known as pleural mesothelioma. The cancer is caused by exposure to a naturally occurring mineral called Asbestos. This mineral is widely popular because of the fire resistant properties. The smaller particles of asbestos reach the pleura during inhalation, which causes inflammation and cellular damage when trapped there.

Asbestos Exposure

Asbestos exposure is the primary reason for pleural mesothelioma. Commonly it is found in the workers of the industries that use Asbestos as the primary object. Common symptoms in the affected individuals were chest pain, cough, and shortness of breath. These symptoms can be identified only after the advanced stage of the disease.

Study

A recent research study led by Karin Schelch and Michael Grusch from MedUni Vienna identified the oncoprotein YB-1 as an attractive therapeutic target in PM and demonstrates that indirect targeting of YB-1 is a promising approach to enhance sensitivity to chemo- and radiotherapy. 

The research builds on findings from earlier this year by the Michael Grusch-led research team at the Center for Cancer Research at MedUni Vienna, Comprehensive Cancer Center at MedUni Vienna, and University Hospital Vienna, which showed that the oncoprotein YB-1 regulates several characteristics of pleural mesothelioma (PM), including cell migration, growth, and death. The new study demonstrates its applicability to drug response as well. Consequently, YB-1 suppression by siRNA led to a marked decrease in tumor growth and an increase in radiation and cisplatin sensitivity.

Target

Trials have previously demonstrated that histone deaceylase inhibitors (HDACi) are efficacious against a variety of tumor cell types. Since there are no pharmaceutical YB-1 inhibitors available on the market, YB-1 was indirectly targeted using entinostat, an HDAC inhibitor that also prevents YB-1 deacetylation, changing the protein’s function.

Our findings provide the basis for the development of novel, clinically feasible therapy approaches

Principal investigator Michael Grusch from the Center of Cancer Research and Comprehensive Cancer Center

Combination Therapy

In addition to demonstrating high synergistic interactions with cisplatin treatment, entinostat demonstrated to be particularly effective against PM cells, which was connected to a large increase in cellular absorption of platinum. The combination of entinostat and cisplatin also produced a greater growth inhibition in a mouse model than did either drug by itself.

These data go hand in hand with another study performed in parallel in Small Cell Lung Cancer where we showed similar synergistic effects between these two drugs

Karin Schelch, MedUni Vienna’s Center for Cancer Research, Comprehensive Cancer Center and Department of Thoracic Surgery at MedUni Vienna and University Hospital Vienna , first author of the present and last author of the parallel study recently published in Clinical Cancer Research.

Publication: Targeting YB-1 via entinostat enhances cisplatin sensitivity of pleural mesothelioma in vitro and in vivo.
Schelch K, Emminger D, Zitta B, Johnson TG, Kopatz V, Eder S, Ries A, Stefanelli A, Heffeter P, Hoda MA, Hoetzenecker K, Dome B, Berger W, Reid G, Grusch M.
Cancer Lett. 2023 Sep 18:216395. doi: 10.1016/j.canlet.2023.216395.

Source: Medical University of Vienna News


Report: Achuth B S

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