Ovarian cancer – novel models and novel targets

Programme stream(s): Cancer discovery / underpinning research , Treatment
Programme session type(s): Bench to bedside

Chair: Iain McNeish, Imperial College London, UK
Speaker: Ahmed Ahmed, University of Oxford, UK
Speaker: Stephen Taylor, University of Manchester, UK
Speaker: Charlie Gourley, University of Edinburgh, UK

14:00-16:00

Room: Carron

The ‘Bench to bedside and back’ sessions are intended to present site-specific research with a cross-cutting approach that covers basic, translational and clinical science. This session will be site-specific to ovarian cancer.

A living biobank of ovarian cancer ex vivo models reveals profound mitotic heterogeneity
Speaker: Stephen Taylor
Affiliation: University of Manchester

Abstract:

High grade serous ovarian cancer (HGSOC) is characterised by TP53 mutation and chromosome instability (CIN). To provide models that support interrogation of CIN mechanisms and to evaluate novel therapeutics, we describe a workflow for generating ex vivo cultures with extensive proliferative potential. Fifteen models from the “living biobank” were validated by p53 profiling, exome sequencing and global transcriptomics, and karyotyped using single-cell whole genome sequencing. Time-lapse microscopy revealed catastrophic and highly heterogeneous mitoses, indicating that analysis of established cell lines grossly underestimates mitotic dysfunction in advanced ovarian cancer. Drug profiling revealed cisplatin sensitivities consistent with patient responses, and cell fate following taxol exposure also showed extensive heterogeneity. By complementing cancer genomics and clinical trials, this workflow has the potential to facilitate personalized approaches to treat HGSOC.