Researchers Identify New Therapeutic Target for Ovarian Cancer
Ovarian cancer has long ranked among the top ten malignant tumors in women, with HGSOC accounting for nearly 70 percent of cases. For clinically challenging cases where complete surgical removal is difficult, the standard treatment strategy remains platinum-based neoadjuvant chemotherapy, the journal Cell reported.
This approach initially achieves high response rates but often leads to drug resistance over time. As a result, the five-year survival rate for patients has stagnated around 30 percent, highlighting the persistent challenges in improving outcomes for HGSOC.
Homologous recombination deficiency (HRD) refers to a condition where cells have impaired ability to repair DNA double-strand breaks through the homologous recombination pathway.
HRD is often associated with an increased risk of genomic instability and cancer development. The presence of HRD in HGSOC not only contributes to its development but also impacts treatment strategies.
Researchers from Tongji Hospital in China and the MD Anderson Cancer Center in the United States initiated a clinical trial of the neoadjuvant PARP inhibitor niraparib for HRD-positive HGSOC based on the concept of reverse translational medicine.
PARP represents a family of enzymes involved in DNA repair. PARP inhibitors block these enzymes, preventing cancer cells, especially those with HRD, from repairing DNA damage, leading to cell death.
During the four-year study, researchers analyzed the unique immune characteristics of the microenvironment in HGSOC, and utilized single-cell transcriptome sequencing and T-cell receptor sequencing to screen tens of thousands of potential targets, according to Gao Qinglei, a professor from the Tongji Hospital.
They identified a novel immune target, eTreg cells, in HRD-positive ovarian cancer, and proposed an immunotherapy strategy that involves depleting eTreg cells and activating immune cells to effectively target and treat the tumors.
They also established HRD mouse models, and discovered that depleting eTregs in the models, with or without PARP inhibition, significantly suppresses tumor growth without observable toxicities, underscoring the potential of eTreg-focused therapeutics for HGSOC and other HRD-related tumors.
"The challenge in treating ovarian cancer lies in cancer cells evading the body's immune defenses. Not only do they escape the surveillance of the immune system, but they also 'capture' immune cells," Gao said.
She noted that by eliminating eTreg cells, the "imprisoned" immune cells can be activated to regain their ability to recognize and kill cancer cells.
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