There are over 15,000 new gynaecological cancers diagnosed each year in the UK, with a doubling in the number of cases of endometrial cancer in the past 15 years. The prognosis for women with ovarian cancer is poor, with only 35% patients still alive five years after diagnosis. The greatest challenges in ovarian cancer research involve diagnosis ovarian cancer earlier, developing novel targeted therapies and generating improved preclinical models of ovarian cancer in which to test these novel therapies. In addition, clinical trials in gynaecological cancer must now focus much more on specific disease subtypes with embedded translational research.
Improving outcomes through innovative clinical trials and better understanding of disease biology
Work focuses on three main areas:
Novel biological therapies for ovarian cancer, especially gene and viral therapies
Oncolytic viruses are potentially powerful new therapies for human malignancy. Iain McNeish's lab has many years experience in evaluating replicating adenovirus, vaccinia virus and HSV vectors in models of ovarian cancer. There is specific emphasis on pathways of cell death induced by oncolytic viruses and role of innate and adaptive immune responses in oncolytic virus efficacy.
Greater understanding of basic disease biology and improving preclinical models
A key question in ovarian cancer is how platinum resistance evolves in recurrent high grade serous ovarian cancer. Through the BriTROC consortium and in collaboration with James Brenton (CRUK Cambridge Institute) and Sean Grimmond, we are investigating changes in structural variation, clonal evolution and DNA damage repair genes (especially members of the homologous recombination pathway) in 300 relapsed high grade serous tumours, using next generation sequencing. Using CRISPR/Cas9 technology, we are also generating novel mouse models of high grade serous ovarian cancer, to allow more robust preclinical assessment of new therapies and disease biology. We also use primary material from patients being treated at the Beatson West of Scotland Cancer Centre, especially primary ascites cultures, wherever possible.
Novel clinical trials
Glasgow has a major reputation for running important and innovative trials in ovarian cancer, run via the Scottish Gynaecological Cancer Trials Group and the CRUK Clinical Trials Unit. Key trials continue this tradition: OCTAVE – a phase I trial of intraperitoneal oncolytic adenovirus ColoAd1 in relapsed ovarian cancer which opened in 2014; BriTROC1 – the largest ever sample collection study in relapsed ovarian cancer; Aerial2 – a phase II translational study of the PARP inhibitor rucaparib in relapsed high grade serous ovarian cancer; NiCCC (Nintedinib in Clear Cell Carcinoma), the first trial of targeted therapies in Clear Cell Carcinomas in the UK, which opened in Spring 2015; HIPROC, a phase I/II study of weekly paclitaxel with the Hedgehog pathway inhibitor LY2940680, which will commence in 2016.
Funding for laboratory research at the WWCRC comes from Cancer Research UK, MRC, Ovarian Cancer Action and the Wellcome Trust. Key academic collaborators include Stephen Tait (CRUK Beatson Institute/University of Glasgow), James Brenton (CRUK Cambridge Institute), Charlie Gourley (University of Edinburgh), Michelle Lockley and Fran Balkwill (Barts Cancer Institute) and the BriTROC collaborative (Glasgow, Cambridge, Edinburgh, Newcastle, Manchester, Leeds, Belfast as well as Barts and Imperial College in London). Industry partners include Clovis, PsiOxus Therapeutics and Virttu Biologics.
Iain McNeish (Wolfson Wohl Cancer Research Centre, WWCRC)
Suzanne Dowson (WWCRC)
Elaine Leung (WWCRC)
Darren Ennis (WWCRC)
Melanie Weigert (WWCRC)
Xinzi Yu (WWCRC)
Malcolm Farquharson (WWCRC)
Josephine Walton (Barts Cancer Institute and WWCRC)
Joana Pinto (WWCRC)
Karen Graham (WWCRC)
Ros Glasspool (BWoSCC – NRS Fellow)
Jim Paul (CRUK Clinical Trials Unit)
Nick Reed (BWoSCC)
Iain McNeish (BWoSCC)
Nadeem Siddiqui (Glasgow Royal Infirmary)