Ovarian cancer: towards more effective drugs with monoclonal organoids

by time news

A group of researchers from European Institute of Oncology and the State University of Milan has developed monoclonal organoids of ovarian cancer, that is, three-dimensional cultures derived in the laboratory from single cells isolated from ascites, the liquid that accumulates in the abdomen in the metastatic phase of this disease. The experiments revealed that in the response to drugs there is a strong difference between the different metastatic cells produced by the same patient, as well as between those obtained from different patients. The results of the study supported by AIRC Foundation were published today on Cell Death and Differentiation, and the implications for precision ovarian cancer care are important.

The discovery

We have discovered a new method to isolate and grow in three dimensions, each individually, the single cells obtained from the metastatic ascites of patients with ovarian cancer. – explains Giuseppe Testa, Laboratory Director of Epigenetics of Stem Cells and Professor of Molecular Biology at the State University of Milan -. We have thus developed the first clonal organoids, or three-dimensional structures developed in the laboratory starting from a single cell. The study of the single clone revealed that the metastatic cells of the same patient are different from each other and that this diversity is the key to finding effective drugs against the spread of the disease. We know that the tumor cells present in the ascitic fluid are very different from each other in terms of their ability to give rise to metastases. Thanks to our method we are now able to identify them and measure their specific sensitivity to drugs, in order to find the most effective molecules to selectively destroy them. Our work opens the way to strong clinical consequences in the medium term, because it offers a powerful precision medicine tool against ovarian cancer, one of the most difficult challenges of contemporary oncology ”.

“The complexity of ovarian cancer, one of the most lethal for the woman, is due to many factors. Among these is the anatomical position, which allows an early spread of the disease in the abdomen through the ascitic fluid. This forms after the tumor, transporting its cells to other organs and giving rise to metastases. In ascitic fluid not all cells are metastatic, but they do not know which ones are and which are not. One of the reasons why effective drugs are currently limited is also the lack of adequate experimental models that allow to analyze, cell by cell, the relevant aspects of the disease from the pathophysiological point of view, such as the metastatic potential. The development of new methods that, starting from the original lesions, patient by patient, identify and analyze the subset of cells that maintain tumor growth is a top priority. Clonal organoids are a fundamental contribution in this direction ”they explain Emanuele Villa and Bianca Barzaghi, IEO researchers who are also first and second authors of the article.

“Organoids in three dimensions have emerged as a tool capable of reproducing the salient characteristics of the tissue or organ of origin and of developing cell subpopulations in the laboratory that reflect the original complexity of the in vivo site from which they derive – continues Pietro Lo Riso, IEO researcher and co-author of the article -. Organoids derived from patients’ metastatic ascites have been described for ovarian cancer, but their polyclonal nature did not allow molecular analysis of individual cells to identify their metastatic potential. We were able for the first time to isolate and propagate organoids from single cells, which allowed us to distinguish between cells resistant to treatment with chemotherapy and cells that are sensitive “.

Monoclonal organoids have allowed us to identify specific and hitherto unknown targets on which to concentrate therapies – concludes Giuseppe Testa-. The next steps are now to identify the drugs to which cells with metastatic potential are sensitive, and then to focus on their “molecular signature”, ie the set of genes that characterize them, to recognize them immediately if they re-emerge. Since we have learned that ovarian cancer responds to chemotherapy, except for a fraction of cells responsible for the recurrence, the ideal therapy will likely be that which combines traditional drugs and drugs targeted against metastatic cells “.

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