PARP Inhibitors Used in ‘One-two Punch’ Strategy to Kill OC Cells in Mouse Models, Study Shows

PARP Inhibitors Used in ‘One-two Punch’ Strategy to Kill OC Cells in Mouse Models, Study Shows
Researchers have developed a two-step approach that harnesses the aging process of cells, allowing breast and ovarian cancers to be effectively targeted and destroyed in cell and mouse preclinical models. The "one-two punch" strategy consists of first treating cancer cells with PARP inhibitors — an anti-cancer therapy used in ovarian and breast cancer — that causes them to age. Those "old" cells are then selectively destroyed with the use of senolytic agents, or small molecules that kill aging cells. The study, “Exploiting interconnected synthetic lethal interactions between PARP inhibition and cancer cell reversible senescence,” was published in the journal Nature Communications. Aging can elicit a variety of stresses that push cells into a process called cellular senescence, where they stop growing and dividing. While this response works to limit the replication of old or damaged cells, the build up of senescent cells in the body may cause a variety of age-related diseases, and cancer. Because senescent cells influence the outcome of a variety of diseases, scientists have actively explored both pro-senescent and anti-senescent therapies. A team of researchers at University of Montreal Hospital Research Centre (CRCHUM), in Canada, found a way to exploit the process of senescence to wipe out breast and ovarian cancer more effectively. The researchers, led by Hubert Fleury, a postdoctoral fellow, Francis Rodier, PhD, and Anne-Marie Mes-Masson, PhD, examined cells with epithelial ovarian cancer (EOC), the most common type of this cancer. They discovered that  EOC cells enter senescence following chemotherapy in combination with PARP inhibitors, a type of targeted therapy used in advanced and recurrent ovarian cancer. Common PARP inhibit
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