Innovative Method Tracks Tumor Evolution to Combat Resistant High-Grade Serous Ovarian Cancer

Ovarian cancer remains one of the most challenging gynecologic cancers to treat effectively due to its tendency to spread at a microscopic level early in its development. Most patients are diagnosed at advanced stages, and although initial treatments like surgery and chemotherapy often lead to remission, the disease frequently recurs, becoming resistant to existing therapies.

Researchers at Memorial Sloan Kettering Cancer Center (MSK) have developed a novel approach to better understand and monitor this recurrence. Their method, called CloneSeq-SV, combines single-cell whole genome sequencing with targeted analysis of structural DNA variations—large-scale genetic alterations that drive cancer progression. This innovative technique allows scientists to track the evolution of tumor cells over time, especially their resistance to treatment.

Using blood samples from 18 patients with high-grade serous ovarian cancer, the team monitored the genetic makeup of circulating tumor cells from diagnosis through recurrence. They discovered that resistant cell populations are often present at the outset, even before treatment begins, and tend to expand after sensitive tumor cells are eliminated. This was made possible by using structural variants as molecular "bar codes," enabling precise tracking of tumor subpopulations in the bloodstream.

The study revealed characteristic features of recurrent tumor cells, including gene amplifications, chromothripsis (a chaotic shattering and reassembly of chromosomes), and whole genome doubling events. Such features offer potential targets for future therapies. For example, one patient responded exceptionally well to trastuzumab deruxtecan—a drug targeting the ERBB2 gene—because therapy eliminated cells lacking ERBB2 amplification, leaving a tumor dominated by ERBB2-positive cells, which could then be specifically targeted.

Looking ahead, the researchers aim to expand their studies to include more patients and tumor samples to refine treatment strategies further. They believe their approach could also be adapted to other cancers characterized by high genetic variability.

This breakthrough provides a promising step toward early detection of treatment resistance and personalized therapies tailored to combat specific tumor cell subpopulations, ultimately aiming to reduce recurrence rates and improve outcomes for ovarian cancer patients.

Source: https://medicalxpress.com/news/2025-10-approach-treatment-resistance-high-grade.html