Research

Chemotherapy Resistance

High grade serous cancer (HGSC) is the most common subtype of ovarian cancer. It is initially very responsive to platinum and taxane chemotherapy but more than 70% patients develop chemotherapy resistance and the disease becomes incurable.

Circumventing resistance is therefore a major unmet clinical need. The Lockley lab has created a panel of chemotherapy resistant HGSC cell lines and are using these to identify novel treatments for chemoresistant disease.

Oncolytic viruses

We aim to improve the utility of oncolytic viruses, whose clinical potential has so far been limited by inflammatory toxicity induced when they are administered systemically.

We showed for the first time that these inflammatory toxicities can be reduced by inhibition of β3 integrin, a cell surface signalling and adhesion protein, without compromising anticancer activity.

We now aim to further improve viral anti-cancer efficacy through combination with immune-modulatory therapies.

Tissue Collection

I set up and continue to lead the Barts Gynae Tissue Bank, This repository of tissue kindly donated by Barts patients is widely used by scientists at the BCI and elsewhere. It is the basis of the ERC funded CanBuild project lead by Prof Balkwill, which is creating innovative and accurate 3D models of the human omentum in high grade serous cancer.

I am Medical Adviser for this project.

Other Activities

• Academic Health Sciences Centre Committee
• NCRI Early Onset Tumours Working Party
• NCRI Gynaecological Cancers Clinical Study Group
• NCRI Ovarian Cancer Subgroup
• Barts Cancer Centre Executive Board
• Barts Cancer CAG Research Governance Committee
• eCancer Medicine online journal Editorial Board
• Member of the Malignant Germ Cell Tumours International Consortium (MaGIC)

Major Funding

• 2016-2020- Cancer Research UK, Advanced Clinician Scientist Fellowship: "New treatments for chemotherapy-resistant high grade serous ovarian cancer, £1.178m
• 2015-2019- Barts Charity, Strategic Research Grant: Discovering new therapies for chemotherapy resistant high grade serous ovarian cancer, £197,545
• 2011-2016- Cancer Research UK, Inflammatory Cytokines and Oncolytic Adenoviruses in Ovarian Cancer, £852,327

Recent Publications

Pathological chemotherapy response score is prognostic in tubo-ovarian high-grade serous carcinoma: A systematic review and meta-analysis of individual patient data Cohen PA, Powell A, Böhm S et al. Gynecologic Oncology (2019) (1)

A multicentre retrospective cohort study of ovarian germ cell tumours: Evidence for chemotherapy de-escalation and alignment of paediatric and adult practice Newton C, Murali K, Ahmad A et al. European Journal of Cancer (2019) 113(7) 19-27

Correction: Safety and utility of image-guided research biopsies in relapsed high-grade serous ovarian carcinoma—experience of the BriTROC consortium (British Journal of Cancer, (2017), 116, 10, (1294-1301), 10.1038/bjc.2017.86) Goranova T, Ennis D, Piskorz AM et al. British Journal of Cancer (2019) 120(7) 868

Mainstreamed genetic testing for women with ovarian cancer: first-year experience. Rahman B, Lanceley A, Kristeleit RS et al. J Med Genet (2019) 56(2) 195-198
https://www.ncbi.nlm.nih.gov/pubmed/29535157

Ovarian cancer in adolescents and young adults. Lockley M, Stoneham SJ, Olson TA Pediatr Blood Cancer (2019) 66(2) e27512
https://www.ncbi.nlm.nih.gov/pubmed/30350916

Histopathologic response to neoadjuvant chemotherapy as a prognostic biomarker in tubo-ovarian high-grade serous carcinoma: updated Chemotherapy Response Score (CRS) results. Böhm S, Le N, Lockley M et al. Int J Gynecol Cancer (2019) (2)
https://www.ncbi.nlm.nih.gov/pubmed/30683759

Copy number signatures and mutational processes in ovarian carcinoma Macintyre G, Goranova TE, De Silva D et al. Nature Genetics (2018) 50(7) 1262-1270

PHLDA1 Mediates Drug Resistance in Receptor Tyrosine Kinase-Driven Cancer Fearon AE, Carter EP, Clayton NS et al. Cell Reports (2018) 22(7) 2469-2481

Deconstruction of a metastatic tumor microenvironment reveals a common matrix response in human cancers. Pearce OMT, Delaine-Smith R, Maniati E et al. Cancer Discov (2017) (1)
https://www.ncbi.nlm.nih.gov/pubmed/29196464

A comparison of p53 and WT1 immunohistochemical expression patterns in tubo-ovarian high-grade serous carcinoma before and after neoadjuvant chemotherapy. Casey L, Köbel M, Ganesan R et al. Histopathology (2017) 71(2) 736-742
https://www.ncbi.nlm.nih.gov/pubmed/28570008

Team

Postdoctoral Researchers in this group
Dr Joseph Hoare, Dr Jayeta Saxena, Dr Vera Silva

Clinical Research Fellows
Dr Helen Hockings, Dr Georgina Wood

Laboratory Technician
Dr Francesco Nicolini

Biography

Academic positions