Cancer is caused by mutations, but not all mutations have the same effects. While some mutations are barely noticeable, others are quite crucial for the growth of cancer cells. One example is BAP1. BAP1 is an important tumor suppressor that is frequently mutated in very aggressive cancers such as uveal melanoma, kidney cancer, bile duct cancer, and malignant mesothelium. To date, there are no treatments specifically targeting these BAP1-mutated cancers.
In a joint project with colleagues from the German Cancer Research Center (DKFZ) and the Technical University of Munich (TUM), two teams from the Medical Faculty of the University of Duisburg-Essen (UDE) and the University Hospital Essen (UK Essen) are investigating new therapeutic options against these mutations. German Cancer Aid is supporting the project with 1.3 million euros.
"Our research has shown that BAP1 mutations are involved in recently discovered signaling pathways. Therefore, we have assembled a research consortium in which different research groups across Germany are investigating these signaling pathways in more detail at different levels, e.g. using cell lines, mouse models and patient:-derived tumor organoids, i.e. mini-tumors grown in the laboratory," explains project leader Dr. Samuel Peña-Llopis from the Department of Ophthalmology at the University Hospital Essen. The main goal of the consortium is to collect solid preclinical data before moving into clinical trials.
A special feature of this consortium is that none of the project leaders in the team already holds a professorial title. The leader of the consortium, Dr. Samuel Peña-Llopis, even has "only" a doctorate so far. But both the research project and the preliminary work of the young research team convinced a large international review panel on behalf of German Cancer Aid to approve and financially support the project application. Such a young team structure is unusual and remarkable, since about 97% of the coordinators in the priority program "Translational Oncology" are professors. That is why Dr. Samuel Peña-Llopis and Dr. Silvia Vega-Rubin-de-Celis, from the Institute for Cell Biology at the University Hospital Essen, as well as the rest of principal investigators from the consortium are particularly proud that the ambitious project was able to convince the German Cancer Aid.
In Germany, more than 15,000 people are diagnosed with renal cell carcinoma each year, while cholangiocarcinoma and mesothelioma affect about 2,000 and 1,500 people, respectively. Choroidal melanoma is a rare cancer, with about 600 new diagnoses annually. Although surgical resection or radiation therapy are effective treatments for uveal melanoma, about half of patients develop metastatic disease within a few years. If the tumor has spread to other organs, the patient's survival time is shortened. New therapeutic approaches are therefore urgently needed - and must be investigated for their effectiveness.
Together with Dr. Titus Brinker and Dr. Rainer Will from the German Cancer Research Center and PD Dr. Kristina Schwamborn from the Technical University of Munich, Dr. Peña-Llopis and Dr. Silvia Vega-Rubin-de-Celis will investigate the success of newly developed therapies over the next three years. The consortium will also study human tumor samples to use machine learning to identify specific biomarkers associated with BAP1 mutations.
"We have already developed a test to identify patients with BAP1 mutations in the clinic. As part of our project, we now want to evaluate new drugs and determine which groups of patients could particularly benefit from precision medicine treatments," Peña-Llopis adds.
Dr. Samuel Peña-Llopis und Dr. Silvia Vega-Rubin-de-Celis, PIs of the new consortium
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