In a study published in the journal Communications of natureResearchers at the Center for Hospital Research at the University of Montreal (CRCHUM) demonstrate, in cells of patients suffering from ovarian cancer, the highest therapeutic efficacy of this "hook followed by an uppercut". ", Based on the manipulation of the state of cellular aging.
Over time, our cells age and enter a phase called cellular senescence. These so-called senescent cells no longer proliferate, accumulate in the body and are responsible for the development of diseases such as cancer. In recent years, the scientific community has tried to cure these conditions related to aging by specifically eliminating senescent cells.
"In the case of ovarian epithelial cancer – the most common and deadly ovarian cancer – we act in two stages: First, we force the premature aging of cancer cells, senescence.This is the" therapeutic hook. "So we launch our" "said Francis Rodier, a researcher at CRCHUM and a professor at the Université de Montréal." This strategy requires excellent coordination of both steps.
The team of researchers, led by Francis Rodier and her colleague Anne-Marie Mes-Masson, found that ovarian cancer epithelial cells enter senescence after chemotherapy with PARP inhibitors. PARPs are enzymes that help repair DNA damage. By blocking them, PARP inhibitors prevent cancer cells from repairing their DNA, disrupting their proliferation, and causing premature aging.
"Our approach could improve the efficacy of chemotherapy with PARP inhibitors and neutralize the systematic resistance associated with this treatment," he said. "Because of our hook-uppercut approach, says Anne-Marie Mes-Masson, a researcher at CRCHUM and a professor at the Université de Montréal.
Future clinical trials in sight?
"Our study was based on cells removed from our biobank samples of CHUM patients with ovarian cancer who agreed to participate in the survey and allowed us to file their biological samples.Our hook-uppercut strategy could also be tested on pre- clinicians of ovarian and breast cancer, which validated its effectiveness, "she says.
Although the results of this study are used to propose clinical trials in ovarian and triple negative breast cancers, it is essential for Francis Rodier to remember that the team used preclinical models, hence the immune system. was absent. "Given the importance of the immune response in humans, we will continue to evaluate our strategy in a context closer to biological reality."
According to the Canadian Cancer Society, 2,800 Canadians were diagnosed with ovarian cancer in 2017 and 1,800 died. In North America, it is the fifth leading cause of death.
About the study
This work was funded by the Montreal Cancer Institute; the Canadian Institutes of Health Research and the Terry Fox Research Institute; the Cancer Research Society in partnership with Ovarian Cancer Canada and the Quebec Research Fund – Health.
The article "Exploring Synthetic Lethal Interactions Interlinked Between PARP Inhibition and Reversible Senescence of Cancer Cells", written by Hubert Fleury and colleagues, appeared in Communications of nature. doi: 101038 / s41467-019-10460-1.
The Montreal University Hospital Research Center (CRCHUM) improves adult health through a continuum of high-level university research that improves the understanding of etiological and pathogenic mechanisms and promotes the development, implementation and evaluation of new preventive strategies, diagnostic and therapeutic. CRCHUM offers a training environment ensuring a succession engaged in excellence research.