Dutch researchers have developed a new experimental protocol that allowed them to culture mini ovarian cancers (organoids) in the lab that retained their three-dimensional structure and captured the cellular diversity seen in patients.
These organoids, which mimic the cellular environment and treatment responses in patients, may be used to further explore the underlying mechanisms of ovarian cancer and open new avenues for therapeutic developments.
The study, “An organoid platform for ovarian cancer captures intra- and interpatient heterogeneity,” was published in Nature Medicine.
Compiling preclinical data has provided crucial information on how cancer cells, and tumors as a whole, behave and work to promote cancer progression. However, for many types of cancer, current preclinical models fail to capture the heterogeneity, or diversity, seen in a single tumor from one patient and between different patients.
As an alternative to cell lines and patient-derived mouse models, researchers have been working on tumor organoid cultures that allow them to create three-dimensional cancer cultures that retain the molecular characteristics of the tumor from which they are derived.
These tiny organoids don’t look like a normal cancer, but the simple cell structures share many of the characteristics of real cancers, including their microenvironment, so researchers can use them to more accurately study cancer.
Thus, researchers at the University of Utrecht in the Netherlands developed a new protocol to develop a long-lasting culture of ovarian cancer organoids derived from patients.
“Developing reliable experimental models that address clinical challenges, such as early detection, tumor recurrence, and acquired chemotherapy resistance, is a high priority in ovarian cancer research,” the researchers wrote.
Using tumor samples from 32 women with all main subtypes of ovarian cancer, the investigators produced 56 organoid lines that replicated the features of the original tumors, as well as the genetic diversity of patients, providing a more complete genetic landscape of ovarian cancer.
To further explore these tumor models, researchers treated them with platinum and taxane-based chemotherapies — carboplatin and paclitaxel — which are commonly used in treatment protocols for ovarian cancer. They also tested the organoids’ sensitivity to other classes of therapies that have been suggested as possible treatments for ovarian cancer.
With this experiment, the researchers were able to separate the organoids into sensitive and resistant to treatment. Interestingly, organoids originating from patients with recurrent disease were more resistant to therapy, while those derived from chemotherapy-sensitive patients were more responsive to treatment.
“Drug-screening assays demonstrated differential drug responses of individual organoid lines,” the researchers wrote, providing evidence of their “potential application for research and personalized medicine.”
The team then attempted to transplant these organoids into mice, and found that they would continue to grow, suggesting they can also be used to address treatment sensitivity in animal models.
These mini ovarian cancers are now available to researchers worldwide as additional models to study the molecular mechanisms of the disease and treatment approaches. They are cataloged here and can be requested by emailing [email protected].
“This living ovarian cancer organoid biobank — available to the research community — faithfully recapitulates ovarian cancer hallmarks, can be subjected to genetic manipulations and to drug screening and opens the door to many avenues of ovarian cancer research,” they concluded.