PRISM
Program: Support the DNA Repair Anomalies Project

Project Team: Prof. Alexandra Leary and Dr. Patricia Kannouche

Predicting Relapses to Improve Survival

Defects in DNA repair promote the development of cancer. These DNA repair defects are responsible for approximately 200,000 cancer deaths per year, particularly among young women. But these defects are also the cancer’s Achilles’ heel.  It has recently been demonstrated that a new class of drugs, PARP inhibitors, can extend patients’ life expectancy. They are an example of targeted therapy, as they selectively kill cancer cells—which have a DNA repair deficiency—while sparing normal cells.

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Project objective:

• To use new, highly sensitive technologies developed at Gustave Roussy to detect signs of relapse as early as possible and enable curative rather than palliative treatment

Project phases:

• Step 1: Conduct a clinical study that will offer early screening to patients who have been treated for ovarian cancer or another cancer with a DNA repair defect. Patients will therefore be monitored every 3 months using “ultra-deep” sequencing technologies designed to analyze every DNA molecule present in the blood. The goal is to conduct this monitoring in a cohort of 500 patients. If a cancerous DNA molecule is detected, the patient will undergo a thorough radiological examination to look for lesions that can be treated surgically and will receive treatment with a PARP inhibitor.  The results from this cohort will be compared to a group of patients receiving standard monitoring.
• Step 2: To understand the mechanisms of resistance to PARP inhibitors, we will analyze tumors from patients who have relapsed despite treatment with a PARP inhibitor. We plan to analyze 150 tumors using single-cell analysis technologies. All molecular data will be integrated, and an artificial intelligence-based image recognition analysis will identify new therapeutic targets. These targets will subsequently lead to the development of anticancer drugs.

Project Impact:

Early identification of relapses in cancers linked to DNA repair defects. Thanks to your support, we will continue to fight rare cancers—particularly those that primarily affect women—and make a truly significant impact on improving survival rates.