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 such as Adaptive Therapy. We also employ drug repurposing approaches and oncolytic viral therapies to tackle drug resistance. In all cases, we aim to translate our laboratory findings into clinical trials for cancer patients.
LiquidCNA: Tracking subclonal evolution from longitudinal liquid biopsies using somatic copy number alterations. iScience (2021) 24(8):102889. PMID: 34401670
Chloroxine Overrides DNA Damage Tolerance to Restore Platinum Sensitivity in High-grade Serous Ovarian Cancer. Cell Death and Disease (2021) 12(4):395. PMID: 33854036
Copy number signatures and mutational processes in ovarian carcinoma. Nat Genet (2018) 50(9):1262-1270. PMID: 30104763
CRISPR/Cas9-Mediated Trp53 and Brca2 Knockout to Generate Improved Murine Models of Ovarian High-Grade Serous Carcinoma. Cancer Res (2016) 76(20):6118-6129. PMID: 27530326
Pharmacological Inhibition of β3 Integrin Reduces the Inflammatory Toxicities Caused by Oncolytic Adenovirus without Compromising Anticancer Activity. Cancer Res (2015) 75(14):2811-21. PMID: 25977332
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. PARP inhibitors are increasingly used in the treatment of ovarian cancer but resistance to these drugs is common and optimal duration of therapy is largely unknown.
Circumventing drug resistance is therefore a major unmet clinical need. The Lockley lab has created a panel of chemotherapy and PARPi resistant HGSC cell lines and animal models. They have already used these models to identify novel treatments for platinum-resistant disease. Adaptive Therapy is a novel treatment paradigm in which drug dose is tailored to the evolution of chemotherapy resistance in individual patients over time. Dr Lockley has used these models to demonstrate the feasibility of adaptive therapy in ovarian cancer and has begun to elucidate the underlying genetic mechanisms. Dr Lockley has successfully translated this approach to the ACTOv clinical trial (Adaptive ChemoTherapy in Ovarian cancer) that will recruit patients from 9 UK sites beginning in 2022.
Rare gynaecological cancers
Dr Lockley has a special interest in rare gynaecological cancers, particularly ovarian germ cell tumours. She is a member of the NCRI early onset working party as well as the International Consortium of Malignant Germ Cell tumours (MaGIC) where she is co-lead for the translational committee and is also developing the next international trial for poor risk germ cell tumours.
Dr Lockley set up and continues 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 with a range of industrial and academic collaborators.
Extracellular matrix educates an immunoregulatory tumor macrophage phenotype found in ovarian cancer metastasis Puttock EH, Tyler EJ, Manni M et al. Nature Communications (2023) 14(7)
The copy number and mutational landscape of recurrent ovarian high-grade serous carcinoma Smith P, Bradley T, Gavarró LM et al. Nature Communications (2023) 14(7)
The avoiding late diagnosis of ovarian cancer (ALDO) project; A pilot national surveillance programme for women with pathogenic germline variants in BRCA1 and BRCA2 Philpott S, Raikou M, Manchanda R et al. Journal of Medical Genetics (2023) 60(7) 440-449
Carvedilol targets β-arrestins to rewire innate immunity and improve oncolytic adenoviral therapy Hoare JI, Osmani B, O’Sullivan EA et al. Communications Biology (2022) 5(7)
Advancing clinical and translational research in germ cell tumours (GCT): recommendations from the Malignant Germ Cell International Consortium Fonseca A, Lobo J, Hazard FK et al. British Journal of Cancer (2022) 127(7) 1577-1583
2022-RA-1443-ESGO Patient decision aids in genetic testing for women with ovarian cancer Sobocan M, Chandrasekaran D, Sideris M et al. (2022) (10) a463.1-a4a463
A novel cell line panel reveals non-genetic mediators of platinum resistance and phenotypic diversity in high grade serous ovarian cancer Hoare JI, Hockings H, Saxena J et al. Gynecologic Oncology (2022) 167(7) 96-106
600P Ethnic and socio-economic status in ovarian cancer patients recruited to clinical trials Palmer KR, El-Shakankery KH, Kefas J et al. Annals of Oncology (2022) 33(10) s820
Addressing the diagnostic and therapeutic dilemmas of ovarian immature teratoma: Report from a clinicopathologic consensus conference Pashankar F, Hanley K, Lockley M et al. European Journal of Cancer (2022) 173(7) 59-70
The Genomic Landscape of Early-Stage Ovarian High-Grade Serous Carcinoma Cheng Z, Mirza H, Ennis DP et al. Clinical Cancer Research (2022) 28(7) 2911-2922For additional publications, please click here
Education and qualifications