Exploiting chromosomal instability across the ovarian–endometrial axis: models, mechanisms and therapeutic targeting

Project Outline

The most aggressive ovarian and endometrial cancers converge on a common phenotype: extensive chromosomal instability (CIN) – ongoing chromosomal changes that generate karyotypic heterogeneity within a tumour, linked to poor patient outcomes. This project asks whether this instability creates shared vulnerabilities we can exploit to find new treatments for patients who currently have few options. 

This project will address three main areas: 

1. Many cancer cell lines were classified before current molecular taxonomies existed, and endometrial cancer lines lack the histotype benchmarking already established for ovarian cancer. Using transcriptomics and machine learning, you will build the first harmonised classification of ovarian and endometrial cancer cell lines, revealing therapeutic targets hiding in plain sight. 
2. You will generate new endometrial cancer models, using modern culture conditions designed to preserve tumour diversity, something older methods often failed to capture. You will analyse these models alongside ovarian cancer models from our Living Ovarian Biobank, challenging both with existing and emerging drugs and using long-read sequencing to map the genomic changes underlying chromosomal instability, linking mechanism directly to treatment response. 
3. Finally, you will address a fundamental open question: where do these cancers actually originate? Using DNA methylation-based lineage tracing, you will compare normal and cancerous tissue from the ovary, fallopian tube and endometrium to trace each tumour’s cell of origin and test whether it shapes biology and treatment response. 

Throughout, you will work within an interdisciplinary team of clinicians and scientists, gaining a thorough grounding in wet-lab and bioinformatic techniques spanning cell biology, translational oncology and genomics. You will benefit from the MCRC’s excellent core facilities, present your work at conferences, and gain experience in patient and public involvement, all within a collaborative, translationally focused, state-of-the-art research environment, while contributing directly to the development of more effective treatments for women with gynaecological cancers. 

Applications for this project are now open. Please complete your application on The University of Manchester website.