Our lab aims to improve treatments for women with ovarian cancer, particularly those that are resistant to chemotherapy. We are interested in developing therapies that can adapt to the evolution of chemotherapy resistance over time. We also use drug repurposing approaches to specifically target chemotherapy-resistant ovarian cancers and to improve the therapeutic benefit of oncolytic viral therapies.
Deconstruction of a Metastatic Tumor Microenvironment Reveals a Common Matrix Response in Human Cancers. Cancer Discov (2018) 8(3):304-319. PMID: 29196464
Beta3 integrin inhibition reduces the inflammatory toxicities induced by oncolytic adenovirus without compromising anticancer activity. Cancer Res (2015) 75(14):2811-21. PMID: 25977332
Chemotherapy Response Score (CRS): Development and validation of a system to quantify histopathological response to neoadjuvant chemotherapy in high-grade serous tubo-ovarian carcinoma. J Clin Oncol (2015) 33(22):2457-63. PMID: 26124480
Paclitaxel resistance increases oncolytic adenovirus efficacy via upregulated CAR expression and dysfunctional cell cycle control. Mol Oncol (2014) 9(4):791-805. PMID: 25560085
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.
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.
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.
Mainstreamed genetic testing in ovarian cancer: patient experience of the testing process. McLeavy L, Rahman B, Kristeleit R et al. Int J Gynecol Cancer (2019) (2)
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
Ovarian cancer in adolescents and young adults. Lockley M, Stoneham SJ, Olson TA Pediatr Blood Cancer (2019) 66(2) e27512
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)
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)
Education and qualifications