New therapeutic targets for the prostate cancer treatment
May 9, 2018
Detected at early stages, prostate cancer is eradicated in 70 to 80% of cases. Unfortunately, its severity may be underestimated at diagnosis, and 20-30% of these patients develop metastases. In order to better manage prostate cancer, Daniel Metzger's team at the IGBMC (CNRS, Inserm, University of Strasbourg) performed an extensive characterization of its evolution which opens new therapeutic perspectives. Results were published on May 9, 2018 in the Journal of Experimental Medecine.
Prostate cancer is the most common male visceral cancer and the third leading cause of cancer death. It progresses over decades, with precancerous lesions followed by adenocarcinomas and metastases.
Since the PTEN and P53 tumor suppressor genes are frequently mutated in prostate cancer in men, Daniel Metzger's team generated mouse models in which PTEN and/or P53 are selectively invalidated in adult prostatic epithelial cells. Their study unraveled key events leading to the development of precancerous lesions.
Following the loss of PTEN, prostatic epithelial cell proliferation is stimulated to form precancerous lesions within a few months. Hyper-proliferation induces replicative stress and a DNA damage response, which in turn lead to a progressive growth arrest with characteristics of cell senescence. However, researchers have shown that these senescent cells secrete a large number of cytokines and chemokines and that by accumulating other mutations, they promote the progression of aggressive tumors.
As side effects and resistance are major drawbacks of current treatments, the development of strategies to eliminate senescent cells from pre-cancerous lesions represents a promising option for prostate cancer treatment.
This study was funded by the ANR, the ARC Foundation for Cancer Research, the Ligue contre le cancer, the Alsace Cancer League, the Assocation pour la recherche sur les tumeurs de la prostate, the Al Bizri Foundation, the China Scholarship Council, the Liliane Bettencourt Foundation, the Centre d’Ingénierie Moléculaire Européen, the Association pour la Recherche à l’IGBMC and the Ministère de l’enseignement supérieur et de la recherche