Researchers from the University of Montreal Hospital Research Centre (CRCHUM) have developed a two-step combination therapy to destroy cancer cells. In a study published online on June 11, 2019 in Nature Communications, they show the superior therapeutic effectiveness of the "one-two punch" on cells of ovarian cancer patients, based on manipulation of the state of cellular aging. Their open-access article is titled “Exploiting Interconnected Synthetic Lethal Interactions Between PARP Inhibition and Cancer Cell Reversible Senescence.” “With time, our cells age and enter a phase called cellular senescence. These senescent cells stop proliferating, build up in the body, and cause the development of diseases such as cancer. In recent years, the scientific community has tried to heal these aging-related pathologies by targeting and destroying senescent cells. "In the case of epithelial ovarian cancer (EOC)--the most common and lethal ovarian cancer--we act in two stages. First, we force the cancer cells to age prematurely, i.e., we force them into senescence. This is the first therapeutic punch. We throw our second punch using senolysis, destroying and eliminating the senescent cancer cells. This strategy requires excellent coordination of the two steps," explained Francis Rodier, PhD, a researcher at the CRCHUM and professor at the Université de Montréal. The team of researchers, led by Dr. Rodier and his colleague Anne-Marie Mes-Masson, PhD, discovered that EOC cells enter senescence following chemotherapy in combination with PARP inhibitors. PARPs are enzymes that help repair damage to DNA. By blocking PARPs, PARP inhibitors prevent cancer cells from repairing their DNA, stop them from proliferating, and cause them to age prematurely.
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