Prostate Cancer – Prof. Mark Rubin (UNIBE) and Dr. Silke Gillessen Sommer (IOSI)

Identification of new targets to treat prostate cancers that are non-responsive to available treatments

Project of Prof. Mark Rubin, University of Bern, and Dr. Silke Gillessen Sommer, Istituto Oncologico della Svizzera Italiana (Oncology Institute of Southern Switzerland)

Prostate cancer is the most common cancer among men, affecting 1 in 8, and is a leading cause of cancer-linked mortality and morbidity. Even though localized prostate cancer is highly treatable with surgery, radiation therapy, or active surveillance, survival rates are poor for men with metastatic disease. Existing hormonal therapies in general induce responses initially, but in the majority of cases, their initial effectiveness fades and eventually fails, leading to metastatic castration-resistant prostate cancer (mCRPC).

In addition to hormonal therapy, one of the most promising current treatment regimes for mCRPC uses radioactive compounds linked to antibodies targeting a cell surface protein on mCRPC cancer cells. Such targeted markers are unique to tumor cells, and the binding of high-energy radioactivity, which acts over a small distance, kills these cells efficiently. Unfortunately, up to 30% of patients fail to express the proteins necessary for the radioactive antibody conjugate to recognize the tumor cells and are thus not eligible for this therapy. In addition, only 50% of the patients that express the appropriate marker protein respond well to the treatment.

The main goal of this project is to nominate new therapeutic targets for patients with mCRPC who are not eligible or resistant to this treatment by identifying new surface proteins unique to prostate cancer. This is a laborious process as many tumors need to be sampled and tested to find proteins uniquely expressed on the surface of the cancer cells and not on normal cells. Such probes will ensure that only the tumor cells are being targeted by the radioactive substance during the treatment. This is particularly important as the probe gets introduced into the bloodstream and not injected locally. Not only would this provide treatment for men who in the moment are not eligible for a theranostic treatment, but it could also lead to the further development of other therapy modalities for these patients using targeted therapies such as CAR-T.