An Innovative Approach to Treating Prostate Cancer

11.03.2024

Prostate cancer is the second leading cause of cancer-related mortality among men worldwide. Although much research concentrates on this form of cancer, the mechanisms underlying resistance to therapy remain poorly understood. Cellular senescence can exert dual effects in tumors, either suppressing or promoting tumor progression. Consequently, the clinical challenge lies in developing therapies that safely enhance senescence in cancer, favoring tumor-suppressive factors.

The study Retinoic acid receptor activation reprograms senescence response and enhances anti-tumor activity of natural killer cells, published by researchers at the Veneto Institute of Molecular Medicine (VIMM), the University of Padua, and the Oncology Research Institute (IOR) of Bellinzona, offer an innovative approach to treating prostate cancer. The promising breakthrough involves cellular senescence and a subset of anti-tumor immune system cells known as natural killer cells (NK cells).

Cellular senescence can halt the proliferation of tumor cells but under specific circumstances, it can also promote resistance to therapy and facilitate the spread of metastases. Researchers of the Molecular Oncology group, led by Prof Andrea Alimonti, Principal Investigator at VIMM and the Oncological Research Institute (IOR) of Bellinzona, and Associate Investigator at VIMM Dr Monica Montopoli began with this idea to develop a new approach to treating prostate cancer.

Taking advantage of a broad chemogenomic screening platform previously developed in the laboratory, researchers identified small molecules capable of triggering senescence in prostate cancer cells, thanks to a screening library of more than 90,000 compounds. Researchers aimed at identifying the retinoic acid receptor agonists, a powerful class of compounds capable of inducing senescence, to stop the cell proliferation of prostate cancer in combination with docetaxel to enhance the anti-tumor effect of the individual compounds. In addition to this, the researchers were able to verify that the combination of adapalene with docetaxel blocks the emergence of therapeutic resistance, which prevents the formation of metastases while activating a powerful anti-tumor immune response.

"Our discovery offers innovative strategies to enhance existing therapies", explains Alimonti. "This combination could promote greater migration of NK cells also in other types of tumors, further improving their anti-tumor activity.”