A new family of biomarkers offers hope for advanced endometrial cancer.
Endometrial cancer is the most common gynecological cancer in Western countries. When diagnosed at an advanced stage or when it recurs, treatment remains challenging and the prognosis is poor. In recent years, new approaches have been added to the treatment arsenal, including targeted therapies and immunotherapy. But a major challenge remains: identifying which patients are most likely to benefit from each of these innovative treatments.
This is precisely the goal pursued by researchers at the Inserm U1086 Anticipe, with support from the Baclesse Center, in this research project. This project focuses on a microRNA, a small molecule naturally present in cells that can regulate the activity of many genes. miRNAs play an important role in the functioning of cancer cells, particularly in their ability to repair DNA damage. This property makes them promising candidates for better understanding sensitivity or resistance to certain targeted therapies.
Promising results from a national clinical trial led by the Baclesse Center
The project is based onthe UTOLA clinical trial, a national study coordinated by Prof. Florence Joly, scientific director of the Baclesse Center, involving some thirty French physicians and the cooperative group GINECO. This trial involved patients with advanced or metastatic endometrial cancer, meaning cancer that had already spread or recurred. After chemotherapy, patients received either a drug called olaparib or a placebo. Olaparib is a targeted therapy already used in certain cancers. It works by interfering with the ability of cancer cells to repair their DNA. Tumor cells often accumulate errors in their DNA and sometimes rely heavily on these repair mechanisms to survive. When a tumor has certain vulnerabilities, blocking these repairs can therefore make the treatment more effective.
Among all patients inthe UTOLA trial, olaparib did not clearly slow the progression of the disease. However, the researchers observed that not all tumors responded in the same way. Some appeared to be more sensitive to treatment, particularly those with a p53 mutation. The p53 protein usually plays a protective role against the development of cancer. When it is abnormal, the tumor is often more aggressive and has a poorer prognosis.
The research team then sought to better understand why some patients might benefit from olaparib. To do so, they analyzed molecules called microRNAs directly in the available tumor samples. MicroRNAs are small regulators of cell function. They can influence how a tumor grows, repairs its DNA, or responds to treatment. A total of 107 tumors from the UTOLA trial were studied. The initial results, presented at the 2026 ESGO European Congress, suggest that a microRNA present in the tumors could help identify the patients most likely to benefit from olaparib. This signal was primarily observed in patients whose tumors had a p53 mutation and low levels of this microRNA. In these patients, the disease progressed more slowly with olaparib than with placebo. In contrast, this benefit was not observed in patients without a p53 mutation, nor in those whose tumors strongly expressed this microRNA.
Prospects for advancing research and ensuring patient survival
The uniqueness of this project lies in the type of biomarker being studied. Research on PARP inhibitors often focuses on genetic alterations or complex DNA repair signatures. Here, the team is exploring the potential of a microRNA that regulates the expression of genes involved in DNA repair as a potential indicator of treatment response. This approach could expand the tools available to better understand endometrial cancers and guide treatment decisions. The results of this project are also expected to yield significant commercial value, centered around a patent application and scientific publications in leading journals.
