Culturing ovarian cancer organoids

Researchers from the Hubrecht Institute (KNAW) and the UMC Utrecht succeeded in developing a new platform for culturing ovarian cancer organoids (mini-organs that resemble the tumor). Ovarian cancer is usually discovered at an advanced stage and has a poor prognosis. The established organoids can be used to study ovarian cancer and may be used in the future to test for drugs against the disease. The results of this research were published in Nature Medicine on the 22^nd of April.

Ovarian cancer organoid | Eierstokkanker organoïde

Cancer in general is characterized by alterations in the genetic material of cancer cells. In ovarian cancer, these alterations are different between patients and even between distinct sites of cancer within one patient. After the initial treatment, which consists of a combination of surgery and chemotherapy, a disease-free period can usually be achieved. Unfortunately, the cancer tends to recur and will in the end become resistant to all available drugs. Due to the differences in DNA-alterations it is difficult to predict if and when this resistance will occur. In clinical practice the patient has to be treated to establish whether the tumor is still sensitive or has become resistant. Ideally, testing a new drug would be performed in the laboratory, prior to its use in a patient. Unfortunately setting up cancer cell cultures for drug testing has largely been unsuccessful.

Ovarian cancer organoid, stained | Eierstokkanker organoïde, aangekleurd

In this new study 56 organoid lines from 32 patients have been established. Most clinical subtypes of ovarian cancer are represented. These new 3D cultures represent the tissue and DNA characteristics of the original tumor. The organoids can be genetically modified and transplanted in mice, providing new opportunities for further research in ovarian cancer. Furthermore, it proved possible to test organoids for chemotherapeutic and targeted drugs. The organoid lines showed, in conjunction with clinical practice, differences in response to these drugs. In some organoid lines the researchers were able to show the occurrence of drug resistance. This new platform can be used for further research and testing effectiveness of personalized systemic therapies for ovarian cancer.

Publication
An organoid platform for ovarian cancer captures intra- and interpatient heterogeneity. Oded Kopper, Chris J. de Witte, Kadi Lõhmussaar, Jose Espejo Valle-Inclan, Nizar Hami, Lennart Kester, Anjali Vanita Balgobind, Jeroen Korving, Natalie Proost, Harry Begthel, Lise M. van Wijk, Sonia Aristín Revilla, Rebecca Theeuwsen, Marieke van de Ven, Markus J. van Roosmalen, Bas Ponsioen, Victor W. H. Ho, Benjamin G. Neel, Tjalling Bosse, Katja N. Gaarenstroom, Harry Vrieling, Maaike P. G. Vreeswijk, Paul J. van Diest, Petronella O. Witteveen, Trudy Jonges, Johannes L. Bos, Alexander van Oudenaarden, Ronald P. Zweemer, Hugo J. G. Snippert, Wigard P. Kloosterman and Hans Clevers. Nature Medicine 2019.

This research is a collaboration between the groups of Hans Clevers and Alexander van Oudenaarden at the Hubrecht Institute, the groups of Wigard Kloosterman, Hugo Snippert and Ronald Zweemer at the UMC Utrecht and other collaborators from the Netherlands Cancer Institute, Leiden University Medical Center, Princess Margaret Cancer Center and the Princess Máxima Center. This research is made possible by KWF, the Gieskes Strijbis Fonds, Vrienden UMC Utrecht & Wilhelmina Kinderziekenhuis and Stand Up To Cancer.

Hans Clevers is group leader at the Hubrecht Institute, professor of Molecular Genetics at the University Medical Center Utrecht and Utrecht University, Research Director of the Princess Máxima Center for Pediatric Oncology and Oncode Investigator.

Alexander van Oudenaarden is director of the Hubrecht Institute, group leader, professor of Quantitative Biology of Gene Regulation at the University Medical Center Utrecht and Utrecht University and Oncode Investigator.