Press Release

10.07.2020

Targeting the proteasome for pharmaceutical drug development

The ALTERNATIVE concept: current proteasome inhibitors inhibit the catalytic activity of the 20S core and thus provide broad inhibition of all proteasome complexes, while the ALTERNATIVE approach selectively targets defined proteasome complexes for therapy of invasive lung cancer. | Image: Silke Meiners, Helmholtz Zentrum München

The Federal Ministry of Education and Research is funding projects on "Target validation for pharmaceutical drug development". Research groups at the Helmholtz Zentrum München have successfully participated in this call and will receive a total of more than 2.3 million euros in funding for their projects. In the project "Alternative proteasome complexes for lung cancer treatment", two scientists from our institute ILBD/CPC and two more institutes of the Helmholtz Zentrum München are joining forces to validate a new target structure.

Prof. Dr. Silke Meiners, Institute of Lung Biology and Disease (ILBD) / Comprehensive Pneumology Center (CPC), is investigating a potential new target for the treatment of invasive lung carcinomas in cooperation with Dr. Georgios Stathopoulos, ILBD/CPC, Dr. Grzegorz Popowicz, Institute of Structural Biology, and Dr. Kamyar Hadian, Institute of Molecular Toxicology and Pharmacology.  The project focuses on a new concept for the inhibition of proteasome complexes for cancer therapy.

The proteasome is a promising therapeutic target structure for tumour treatment. As the central protein degradation system of the cell, it controls various cellular processes such as growth and survival of the cells. Proteasomes consist of a family of distinct enzymatic complexes, all of which share a proteolytic core, the 20S proteasome, but are distinguished by different activators. Each of these proteasome activators plays a defined role in the regulation of central cellular processes. Proteasome inhibitors, such as the drug Velcade™, inhibit the catalytic activity of the core 20S proteasome and show very good efficacy in the treatment of multiple myeloma. However, their efficacy in solid tumours is limited due to their high systemic toxicity. Silke Meiners' research group was able to identify an alternative proteasome complex as an important regulator of lung tumour growth and invasion. In the now funded project "Targeting Alternative Proteasome Complexes for Lung Cancer Therapy", the inhibition of this proteasom complex is to be validated as a new therapeutic target for the treatment of invasive lung carcinomas. The team led by Silke Meiners as head of the "Proteasome function in lung biology and disease" research group, Georgios Stathopoulos as an expert in the molecular analysis of lung cancer, Grzegorz Popowicz with his expertise in structural analysis and drug discovery and Kamyar Hadian as head of the Assay Development and Screening Platform at the Center will receive funding of almost one million euros for this task.