Prostate cancer: innovative therapeutic approach identified at IOR
Institute of Oncology Research
Scientists at the Institute of Oncology Research (IOR, affiliated with USI and a member of Bios+) in collaboration with the Veneto Institute of Molecular Medicine (VIMM) and the University of Padua have made a significant discovery by identifying a new therapeutic approach for the treatment of prostate cancer. The study is published in the prestigious journal Cancer Cell.
Background
Prostate cancer is the most common cancer among men. Although approaches such as radical prostatectomy, chemotherapy, and radiation therapy are often effective initially, resistance to therapy may subsequently arise. Despite active research in prostate cancer, the mechanisms underlying resistance to therapy are still poorly understood. Much of the treatment currently used in the clinic initially induces an irreversible arrest of cell growth, known as cellular senescence.
This is the context of a study by a group of scientists from the Institute of Oncology Research (IOR) in collaboration with the Veneto Institute of Molecular Medicine (VIMM) and the University of Padua (Italy), who have identified a novel approach to treating prostate cancer that involves cellular senescence and a subset of anti-tumor immune system cells known as Natural Killer (NK) cells.
The discovery
Cellular senescence may initially halt cancer cell proliferation, however, under specific circumstances, it may promote resistance to therapy and facilitate metastatic spread.
In fact, researchers in the Molecular Oncology group, led by Prof. Andrea Alimonti, Principal Investigator at IOR and VIMM, and Prof. Monica Montopoli, Associate Investigator at VIMM, started from this idea to develop a new approach to treat prostate cancer.
"The combined effect of this class of drugs with Docetaxel is revolutionary. We have identified a metabolic deficit in the retinoic acid production pathway in prostate cancer. The combination of these agonists with Docetaxel has a synergistic effect in inhibiting tumor proliferation," explain the study's first authors Manuel Colucci, a researcher at the IOR, and Silvia Bressan and Federico Gianfanti, also researchers at the IOR and formerly PhD students at VIMM and the University of Padua. "In addition, our studies have further investigated the effects of combining Adapalene, a third-generation retinoic acid receptor agonist, with Docetaxel on the involvement of the immune system in fighting the tumor, showing that this specific combination not only enhances the antitumor effect of each drug, but also activates an NK-cell-mediated antitumor immune response," adds Sara Zumerle, a researcher at VIMM and the University of Padua and recipient of a research grant from the Veronesi Foundation, another first author of the study.
Perspectives
Through extensive chemistry-genomics (chemogenomic) screening conducted on approximately 90,000 compounds, researchers have identified retinoic acid receptor agonists as a potent class of compounds capable of inducing senescence, and thus able to halt prostate cancer cell proliferation. Their combination with Docetaxel is able to enhance the antitumor effect of the individual compounds. In addition to this, the researchers were able to verify that the Adapalene-Docetaxel combination blocks the phenomenon of therapeutic resistance, prevents metastasis formation, and at the same time activates a potent antitumor immune response.
"Our discovery paves the way for innovative strategies that can enhance existing therapies," explains Prof. Alimonti. "This combination could also promote increased migration of NK cells in other tumor types, further enhancing their antitumor activity."
A follow-up project resulting from these findings is already underway in collaboration with IBSA Institut Biochimique SA about the study of these processes in other pathophysiological conditions.
At IOR, the project was implemented with funds from the Swiss Cancer League and the Swiss National Science Foundation (SNSF).
