GYNAECOLOGY

 

WHERE TO FIND US

• The Christie NHS Foundation Trust
• MCRC building
• MFT - Saint Mary’s Hospital
• The University of Manchester

Research into gynaecological oncology in Manchester is spread across multiple hospital trusts and locations.

Within discovery research, our scientists are looking at chemotherapy drugs that target different aspects of the cell cycle. Our experiments probe how anti-mitotic agents such as paclitaxel causes cell death, with an overall aim of trying to predict response, overcome resistance and ultimately improve the efficacy of these drugs. A collaboration with Drug Discovery is focused on defining which ovarian cancers will be sensitive to novel inhibitors targeting PARG. One group is focused on DNA damage responses, and their regulation by ubiquitylation pathways in particular. We are also exploring other relevant aspects of cell biology, including the way in which integrin trafficking pathways are manipulated by cancer cells in order to drive invasion and metastasis.

To help drive our discovery research, we are building a living biobank of ovarian cancer models. Biopsies from cancer patients treated at The Christie are processed to generate cultures of proliferating tumour cells, which are suitable for both cell biology studies and drug sensitivity profiling. By correlating the behaviour of the cultured cells with clinical data, our vision is that these models may in the future serve as patient avatars, allowing us to design truly personalised treatment options.

Translational research aims to convert knowledge of the DNA damage response and angiogenesis into clinical benefits for patients with ovarian cancer. Our clinical group is interested in exploring the link between obesity and endometrial cancer, with a view to developing new treatment and prevention strategies, and is assessing the impact of other risk factors such as Lynch Syndrome. We also carry out trials of novel agents, in particular anti-angiogenic drugs, in ovarian cancer patients. Other research interests include human papillomavirus (HPV)-associated lower genital tract neoplasia, particularly cervical dysplasia and cervical cancer. 

CURRENT RESEARCH QUESTIONS

  • How can we exploit mitosis and the spindle checkpoint?
  • What is the role of ubiquitylation within and beyond the DNA damage response?
  • How do we translate our knowledge of mitosis and DNA damage repair pathways into clinical benefits for patients with ovarian cancer?
  • How do integrins drive invasion in ovarian cancer?
  • Can we develop biomarkers to optimise anti-angiogenic therapies?
  • What are the best prevention and early detection strategies for endometrial and ovarian cancer?

KEY PUBLICATIONS

MYC Is a Major Determinant of Mitotic Cell Fate.
Topham C, Tighe A, Ly P, Bennett A, Sloss O, Nelson L, Ridgway RA, Huels D, Littler S, Schandl C, Sun Y, Bechi B, Procter DJ, Sansom OJ, Cleveland DW, Taylor SS.
Cancer Cell. 2015 Jul 13;28(1):129-40. doi: 10.1016/j.ccell.2015.06.001.

Systematic E2 screening reveals a UBE2D-RNF138-CtIP axis promoting DNA repair.
Schmidt CK, Galanty Y, Sczaniecka-Clift M, Coates J, Jhujh S, Demir M, Cornwell M, Beli P, Jackson SP.
Nat Cell Biol. 2015 Nov;17(11):1458-1470. doi: 10.1038/ncb3260. 

Ovarian Cancers Harbor Defects in Nonhomologous End Joining Resulting in Resistance to Rucaparib.
McCormick A, Donoghue P, Dixon M, O'Sullivan R, O'Donnell RL, Murray J, Kaufmann A, Curtin NJ, Edmondson RJ.
Clin Cancer Res. 2017 Apr 15;23(8):2050-2060. doi: 10.1158/1078-0432.CCR-16-0564. 

A MAPK-Driven Feedback Loop Suppresses Rac Activity to Promote RhoA-Driven Cancer Cell Invasion.
Hetmanski JH, Zindy E, Schwartz JM, Caswell PT.
PLoS Comput Biol. 2016 May 3;12(5):e1004909. doi: 10.1371/journal.pcbi.1004909. eCollection 2016 May

Monocarboxylate Transporter 1 (MCT1) is an independent prognostic biomarker in endometrial cancer.
Latif A, Chadwick AL, Kitson SJ, Gregson HJ, Sivalingam VN, Bolton J, McVey RJ, Roberts SA, Marshall KM, Williams KJ, Stratford IJ, Crosbie EJ.
BMC Clin Pathol. 2017 Dec 28;17:27. doi: 10.1186/s12907-017-0067-7

PARP inhibitors in platinum-sensitive high-grade serous ovarian cancer.
Morgan RD, Clamp AR, Evans DGR, Edmondson RJ, Jayson GC.
Cancer Chemother Pharmacol. 2018 Apr;81(4):647-658. doi: 10.1007/s00280-018-3532-9. 

Association of Mismatch Repair Mutation With Age at Cancer Onset in Lynch Syndrome: Implications for Stratified Surveillance Strategies.
Ryan NAJ, Morris J, Green K, Lalloo F, Woodward ER, Hill J, Crosbie EJ, Evans DG.
JAMA Oncol. 2017 Dec 1;3(12):1702-1706. doi: 10.1001/jamaoncol.2017.0619.

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