Including cancers of the cervix, endometrium, ovaries, vagina, and vulva
Gynaecological cancer research covers five types of cancer that starts in the woman’s reproductive system, including cancers of the cervix, endometrium, ovaries, vagina, and vulva. Research in Manchester covers the spectrum of basic, translational and clinical research with the aim to develop new strategies and techniques to detect and treat gynaecological cancers.
Within discovery research, Manchester scientists are looking at chemotherapy drugs that target different aspects of the cell cycle. Scientists are probing 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 at the Cancer Research UK Manchester Institute is focused on defining which ovarian cancers will be sensitive to novel inhibitors targeting poly(ADP-ribose) glycohydrolase (PARG).
One group is focused on DNA damage responses, and their regulation by ubiquitylation pathways in particular. In addition, the group is 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 discovery research, the group 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, the vision is that these models may in the future serve as patient avatars, enabling the design of truly personalised treatment options.
Research in the Endometrial and Womb Cancer research group is focused on the screening, prevention and early detection of gynaecological cancers.
The rising prevalence of obesity is driving an explosion in endometrial cancer diagnoses in the UK, already the 4th most common cancer in women. Understanding the mechanism underpinning endometrial carcinogenesis is an important stepping stone to novel prevention strategies. The group has tested the biological impact of weight loss, insulin sensitising drugs and progestin hormone treatments to assess their suitability for large scale endometrial cancer prevention trials and develop intermediary biomarkers of response. Ongoing work in this area includes the development of a risk prediction model, incorporating obesity, insulin resistance, reproductive and genetic biomarkers to enable personalised risk assessment for targeted screening and prevention interventions.
Research on Lynch Syndrome
Lynch syndrome is a hereditary cancer predisposition syndrome caused by inherited faults in the DNA mismatch repair (MMR) genes, leading to a high lifetime risk of colorectal, endometrial and other cancers. Knowing that a person has Lynch syndrome can enable bowel screening and aspirin chemoprevention, interventions that have been shown to save lives. The group showed that 3% of endometrial cancers are caused by Lynch syndrome and how best to identify them. Testing everyone is best because they cannot always be identified by age, family history or tumour biology.
In 2020, work by the group led to new NICE guidelines that recommend the universal screening of endometrial cancer patients for Lynch syndrome. Ongoing work in this area includes an appraisal of the effectiveness of gynaecological surveillance and risk reducing surgery in Lynch syndrome.
Preventing and diagnosing gynaecological cancers at an early stage remains a significant challenge that our group is keen to address. We have developed minimally invasive early detection tools for ovarian, endometrial and cervical cancer that are now being tested in large diagnostic test accuracy studies. Ongoing work in this area includes the study of urinary HPV testing for cervical screening and its ability to improve uptake of cervical screening.
Discover more about the Prevention and Early Detection research developed by Professor Emma Crosbie, including a urine-test to detect pre-cancerous biomarkers in ‘Driving Changes in Cervical Screening‘, an article from Cancer Futures Issue 2.
- Preventing breast and endometrial cancer through total dietary replacement-induced weight loss in women with obesity: a feasibility study with biomarker endpoints
- Minimally-invasive biomarkers for ovarian cancer detection: blood, urine and vaginal fluid
- Personalised risk prediction tools incorporating obesity, insulin resistance, reproductive and genetic risk scores for targeted prevention and screening interventions
- Symptom awareness and help seeking behaviour in women with postmenopausal bleeding at risk of endometrial cancer
- Diagnostic models for endometrial cancer: systematic review of the literature, external validation of published models and development of a novel risk score for women presenting to secondary care with postmenopausal bleeding
- Developing Tests for Endometrial Cancer Detection (DETECT): a diagnostic test accuracy study of urine and vaginal biomarkers for endometrial cancer detection in 2,000 women presenting to secondary care with postmenopausal bleeding
- Proteomic biomarkers for endometrial cancer detection in women with postmenopausal bleeding: biomarker discovery by SWATH-MS and clinical validation
- Prognostic biomarkers for endometrial cancer: discovery, testing and validation
- Urine HPV testing for cervical screening: (1) a diagnostic accuracy study in primary care and colposcopy referral populations and (2) a randomised controlled trial of urine self-sampling kits offered to cervical screening non-attenders
- Evidence synthesis to establish the clinical effectiveness and cost-effectiveness of gynaecological surveillance and risk reducing surgery in Lynch syndrome
- Weight loss combined with intrauterine progestins for the conservative management of atypical hyperplasia and endometrial cancer: feasibility study and search for predictive biomarkers
- Self examination and symptom awareness in women with vulval precancerous conditions for the early detection of vulval cancer
- Sexual wellbeing in endometrial cancer survivors
Lynch syndrome and endometrial cancer: How our research led to new NICE guidance
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