Precision targeting of drug resistance in primary cancer cell models

Abstract: Our goal is to understand mechanisms of drug sensitivity and resistance in individual cancers. Through this knowledge, we aim to identify new effective cancer precision medicine strategies that can be explored in the clinic. Our work is centred around studies of cancer cells and how their subpopulations respond to different treatments. We primarily study three types of cancer, acute myeloid leukaemia, high grade serous ovarian carcinoma and glioblastoma. A particular focus is the mechanisms of resistance to current therapies and how they can be overcome.
To accomplish our goals, we are actively working on improving primary cell culture models with the goal of generating increasingly relevant models for our studies. Critical for drug resistance studies is to understand the heterogeneity of a cancer cell population and what the identity of the cells that survive drug treatments are. We combine short-term high throughput single cell analyses using microscopy and flow cytometry, with (low throughput) long-term assays to follow cells that emerge after treatments. To further identify and understand mechanisms of treatment sensitivities and resistance, we use CRISPR screening and lineage tracing. Ultimately, we search for molecular features that can predict sensitivity to a given treatment and therefore could be used to stratify patients in the clinic.
In this presentation, I will show examples of how we use advanced primary cancer cell models, high throughput methodologies and laboratory automation to identify new potential vulnerabilities of drug resistant cancers and how they could be predicted.