From Early Lesions to Therapy Resistance: Exploring New Frontiers in Ovarian Cancer

Details

High-grade serous ovarian cancer (HGSOC) is the most lethal gynaecological malignancy, with survival rates that have changed little in decades. Two persistent challenges contribute to this: most cases are diagnosed only at an advanced stage, and even when initial chemotherapy is effective, relapse with drug-resistant disease is common. Tackling both late detection and therapy resistance remains a major unmet need.

Within our programme there are several complementary strands of work addressing these challenges. One area seeks to understand the earliest stages of HGSOC development in the fallopian tube, where pre-cancerous serous tubal intraepithelial carcinoma (STIC) lesions provide a potential window for earlier detection. Another focuses on how altered DNA-damage response pathways and novel protein-modifying systems contribute to chemoresistance in established tumours. Together, these strands offer opportunities to generate new insights into disease biology and to identify targets for improved diagnosis and treatment.

Potential projects in this space could include developing and characterising patient-derived or organoid models of early lesions to study their secreted factors as candidate biomarkers, or interrogating post-translational modifications and repair pathways that enable tumour cells to withstand chemotherapy. Findings from such work would be integrated with clinical material from Manchester’s partner hospitals to ensure translational relevance.

You will receive training in state-of-the-art molecular biology, cell biology, proteomics, and translational cancer research methods, and have scope to tailor the project within these themes. By investigating either early lesion biology or mechanisms of therapy resistance, the research has potential to contribute to earlier detection, better patient stratification and the development of more effective, less invasive treatments for women with the hardest-to-treat ovarian cancers.

Further information on our research and institute can be found here:

Genome Stability Lab (GSL)

Entry requirements

Applicants are expected to hold (or about to obtain) a minimum upper second-class undergraduate honours degree (or equivalent) in Biochemistry, Cancer Sciences, Biotechnology, or Cell Biology or another related subject area. Research experience in Molecular Biology, Biochemistry, Cell Biology and Ovarian Cancer is desirable.

Before you Apply

Applicants must make direct contact with preferred supervisors before applying. It is your responsibility to make arrangements to meet with potential supervisors, prior to submitting a formal online application.

How To Apply

For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/). Informal enquiries may be made directly to the primary supervisor.

On the online application form select PhD Cancer Sciences.

For international students, we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences. For more information please visit https://www.bmh.manchester.ac.uk/study/research/programmes/integrated-teaching/

Your application form must be accompanied by a number of supporting documents by the advertised deadlines. Without all the required documents submitted at the time of application, your application will not be processed and we cannot accept responsibility for late or missed deadlines. Incomplete applications will not be considered.

If you have any queries regarding making an application please contact our admissions team FBMH.doctoralacademy.admissions@manchester.ac.uk.

Equality, Diversity and Inclusion

Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website https://www.bmh.manchester.ac.uk/study/research/apply/equality-diversity-inclusion/

Funding Notes

Applications are invited from self-funded students. This project has a Band 3 fee. Details of our different fee bands can be found on our website https://www.bmh.manchester.ac.uk/study/research/funding-fees/fees/

References

1. Wang Z , Foster BM , da Costa IC , Wu Y , Behera D , Conte F , Trotter EW , Cabello-Lobato MJ , Choudhary S , Wiener R ,Beli P, Smith DL , Banks WH, Bagley S , McKee S , Minnis M, Meyer S , Chaplin AK, Dörner W, Mootz D , Hagan IM , Galanty Y, Larrosa I, Cliff MJ, Schmidt CK. UFMylation orchestrates chromatin engagement of core NHEJ components to promote DNA double-strand break repair. bioRXiv (2025). https://www.biorxiv.org/cgi/content/short/2025.06.16.659844v1

2. Schmidt CK*, Medina-Sánchez M*, Edmondson RJ, Schmidt OG*. Engineering microrobots for targeted cancer therapies from a medical perspective. Nature Communications (2020). DOI: 10.1038/s41467-020-19322-7.

3. Xu H, Medina-Sánchez M*, Zhang W, Seaton M, Brison DR, Edmondson RJ, Taylor SS, Nelson L, Zeng K, Bagley S, Ribeiro C, Restrepo LP, Lucena E, Schmidt CK*, Schmidt OG*. Human spermbots for patient-representative 3D ovarian cancer cell treatment. Nanoscale (2020). DOI: 10.1039/D0NR04488A.

4. Cabello-Lobato MJ, Jenner M, Cisneros-Aguirre M, Brüninghoff K, Sandy Z, da Costa IC, Jowitt TA, Loch CM, Jackson SP, Wu Q, Mootz HD, Stark JM, Cliff MJ, Schmidt CK. Microarray screening reveals two non-conventional SUMO-binding modules linked to DNA repair by non-homologous end-joining. Nucl. Acids Res. (2022). 50(8), 4732.

5. Osborne HC, Foster BM, Al-Hazmi H, Meyer S, Larrosa I, Schmidt CK. Small-molecule inhibition of CBX4/7 hypersensitises homologous recombination-impaired cancer to radiation by compromising CtIP-mediated DNA end resection. Cancers (2024). 16 (11), 2155.