Ovarian cancer clinical trials could soon evaluate a promising new treatment approach developed by researchers at the University of Montreal Hospital Research Centre (CRCHUM). Published in the journal Nature Communications, the study describes a two step combination therapy designed to destroy cancerous ovarian cells by manipulating the process of cellular aging. The researchers call it a “one two punch” strategy, and early results in preclinical models suggest it could significantly improve outcomes for patients with one of the most lethal forms of gynecological cancer. If the approach performs as expected in human studies, it has the potential to reshape how ovarian cancer clinical trials design combination therapy protocols going forward.<\/p>\n
To understand how this therapy works, it helps to understand the biology of cellular aging. With time, human cells age and enter a phase called cellular senescence, a state in which they stop dividing and begin to accumulate in the body. This buildup of senescent cells contributes to the development of numerous diseases, including cancer. In recent years, researchers have explored whether targeting and eliminating senescent cells could offer a pathway to treating aging related conditions and improving outcomes in ovarian cancer clinical trials.<\/p>\n
In the case of epithelial ovarian cancer (EOC), the most common and lethal form of ovarian cancer, the CRCHUM team applied this concept in a deliberate two phase sequence. The first step forces cancer cells into premature senescence using a combination of chemotherapy and PARP inhibitors. The second step destroys the now senescent cancer cells before they can cause further damage.<\/p>\n
“This strategy requires excellent coordination of the two steps,” explained Francis Rodier, a researcher at the CRCHUM and professor at the Universit\u00e9 de Montr\u00e9al. “We force cancer cells to age prematurely. That is the first therapeutic punch. We throw our second punch by destroying and eliminating them.”<\/p>\n
PARP enzymes are responsible for repairing damage to DNA. By blocking these enzymes, PARP inhibitors prevent cancer cells from fixing their own DNA, which stops them from proliferating and causes them to enter a state of premature aging. The CRCHUM team discovered that EOC cells undergo senescence following treatment with chemotherapy in combination with PARP inhibitors, creating the conditions necessary for the second step of the therapy.<\/p>\n
“Thanks to our one two punch approach, we have managed to destroy senescent EOC cells in preclinical ovarian cancer models,” said Anne Marie Mes-Masson, a researcher at the CRCHUM and professor at the Universit\u00e9 de Montr\u00e9al. “Our approach could improve the effectiveness of chemotherapy in combination with PARP inhibitors and counteract the systematic resistance that develops with this treatment.”<\/p>\n
The research was conducted using cells drawn from a biobank of samples collected from CHUM ovarian cancer patients who agreed to participate in research and allow their biological specimens to be stored. The one two punch strategy was also tested on preclinical breast cancer models, allowing the team to validate its effectiveness across more than one cancer type.<\/p>\n
Although these results are being used to propose future ovarian cancer clinical trials, the researchers are careful to note the limitations of preclinical work. The models used did not include an immune system, which plays a critical role in how treatments perform in human patients.<\/p>\n
“Given the importance of the immune response in humans, we need to continue evaluating our strategy in a context closer to biological reality,” said Rodier.<\/p>\n
According to the Canadian Cancer Society, 2,800 Canadian women were diagnosed with ovarian cancer in 2017 and 1,800 died from the disease, making it the fifth leading cause of cancer death in North America. The development of more effective combination therapies, and the ovarian cancer clinical trials needed to validate them, represents one of the most urgent priorities in gynecological oncology research today.<\/p>\n
Translating a preclinical discovery into an approved therapy requires a rigorous multi phase clinical trial program. Ovarian cancer clinical trials demand sites with the oncology expertise, patient access, and regulatory infrastructure to enroll participants safely and collect high quality data across diverse populations.<\/p>\n
FOMAT supports oncology research across the United States, providing sponsors and CROs with access to experienced investigator teams and diverse patient populations. Our sites are equipped to participate in the kind of complex, multi step combination therapy studies that discoveries like this one will eventually require. To learn more about our active studies<\/a> or our oncology capabilities<\/a>, visit fomatmedical.com.<\/p>\n \nFor More Information<\/h4>\n