Dr Kenny Chitcholtan is a senior research fellow at the Department of Obstetrics and Gynaecology, The University of Otago, Christchurch, New Zealand. He is particularly interested in working with 3D ovarian cancer models (specifically organoids), and has experience working with these in high-grade serous ovarian cancer. Cure Our Ovarian Cancer received a generous private donation of $75 000 to allow us to fund a pre-clinical (laboratory) project using organoid cancer models in low-grade serous carcinoma.
Organoid cancer models are a relatively recent area of cancer research. To our knowledge, the first published instance of a low-grade serous carcinoma organoid was in May 2019 in the Netherlands. Compared to traditional cell lines, which are essentially collections of flat cells in a Petri dish, 3D models have a more complex structure that better reflects the cancer in vitro (i.e. the cancer inside a patient). There are two main types of 3D cancer models, xenographs (where the cancer is implanted into a mouse model) and organoids (which do not require an animal to grow). Aside from animal rights considerations, organoids are thought to generally be easier and cheaper to grow and maintain than xenographs though they do not have their own vascular system. General cancer research suggests that 3D models are able to be better predict whether a drug will work in patients compared to traditional cell line drug screenings.
Preclinical research is an important building block to finding new treatments. The more researchers learn about low-grade serous, and the better the models they have to predict it’s behaviour, the greater chance of choosing a drug or drug combination that will work when tested in women in a clinical trial. Dr Chitcholtan hopes that organdoids could provide a much better model of cancer behaviour to predict drug response in low-grade serous carcinoma than the cell lines that are currently used.
In general, low-grade serous cell lines can be challenging to grow because it is by nature a slow growing cancer. In some instances it can take up to six months to produce one cell line. Dr Chitcholtan intends to trial different ways to speed up the cancer growth to create an organoid more quickly without losing important characteristics of the cancer. Once he has developed stable organoid models he will apply a MEK inhibitor drug to the organoid. By examining various proteins expressed by the cancer he hopes to find drug combinations that could work synergistically with the MEK inhibitor to improve cancer response rates.
*Oded Kopper1,2, Chris J. de Witte et al., “An organoid platform for ovarian cancer captures intra- and interpatient heterogeneity”. NATURE MEDICINE ;VOL 25; MAY 2019; 838–849
August 15 2019