A groundbreaking multi-institutional study has uncovered a hidden mechanism potentially responsible for the high recurrence rate in ovarian cancer patients, raising concerns about a newly suspected form of residual disease.

Despite decades of research, the overall survival (OS) rate for advanced ovarian cancer has remained stagnant, largely due to its recurring nature. While nearly 80% of patients respond well to initial chemotherapy and surgeries, many experience relapse until now, with little explanation as to why.

A new study published in Clinical Cancer Research, a journal of the American Association for Cancer Research, sheds light on the mystery by identifying a previously overlooked threat: Minimal Residual Disease (MRD).

Hidden Cancer Cells Detected Despite Clean Scans
Led by TeamLab, a collaborative effort including the University of Texas MD Anderson Cancer Center, Memorial Sloan Kettering, Johns Hopkins, Dana-Farber, and MIT’s Koch Institute, the study found that nearly half of ovarian cancer patients in remission still harbor hidden cancer cells, even when imaging shows no signs of disease.

Using advanced proteomic profiling and spatial transcriptomics, researchers analyzed MRD samples in unprecedented detail. They identified several druggable targets and uncovered biological pathways such as immune evasion, epithelial-mesenchymal transition, and hypoxia signaling that may allow cancer cells to survive treatment and evade detection.

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Breakthrough Blood Test Offers Hope
A major part of the study focused on circulating tumor DNA (ctDNA) tiny fragments of cancer DNA in the bloodstream as a minimally invasive tool to detect MRD. The use of ctDNA offers a powerful way to monitor disease progression, personalize treatment, and detect recurrence without the need for additional surgery.

“This research represents a critical shift in how we understand and monitor ovarian cancer,” said a spokesperson from TeamLab. “It’s not just about what we can see on scans, but what we’re missing at the molecular level.”

Second-Look Laparoscopy Reveals What Scans Miss
The researchers also employed a less invasive surgical technique called second-look laparoscopy (SLL) after chemotherapy and blood testing. Despite scans showing no evidence of disease, SLL revealed that 42% of patients still had lingering cancer cells, proving that conventional tests often miss MRD.

This study is part of a broader effort to understand MRD across multiple cancer types, including ALK-positive lung cancer and acute myeloid leukemia. Ongoing clinical trials are now using MRD detection as a primary endpoint, testing new immunotherapies aimed specifically at eradicating these hidden cancer cells.

Outlook
With MRD emerging as a critical factor in ovarian cancer recurrence, the research opens new doors for drug development and early intervention strategies

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