Developing Human Glioma OrganDot Cultures

Advanced investigations determining how cancers grow and resist treatment inevitably involve experimentation in animals which have had human cancer cells seeded into an appropriate organ or which have been genetically modified to develop cancer. Similarly, the use of such animal models is the current gold-standard to test new anti-cancer drugs. Animals models are preferably used as they can provide a three-dimensional (3D) tissue environment resembling to some extent the clinical cancers in patients. This 3D environment, involving interactions of multiple different types of (cancer and non-cancer) cells is a critical determinant of the aggressiveness of a cancer and its responsiveness to therapy. These properties are simply not replicated in standard laboratory culture of cancer cells which are recognised as poor models to predict of cancer behaviour and response.

This project will use new, proprietary methods to generate 3D mixed cell cultures, OrganDots, established from individual cells derived from patient tumour tissue. These OrganDots will recapitulate the cancer cells together with non-cancer cells from the patient in a way that better reflects cancer biology and drug-responsiveness. This project will generate OrganDots from the most frequent and most aggressive primary brain cancer in adults, Glioblastoma (GBM). The conditions for growth of GBM-derived OrganDots will be optimised and their relevant biology characterized. Their ability to predict in a culture, the matched patient responses to standard GBM therapy will be assessed, as will their response to new, experimental therapies. Thus, OrganDots may be useful for both personalized medicine (predicting a patient's response to therapy) and developing new drugs. Critically if the project is successful with one of the most challenging of human cancers, GBM, the OrganDot approach can be translated for use in a wide range of solid cancer types, contributing significantly to reducing animal experimentation.