Research

Drug Resistance

High-grade serous cancer (HGSC) is the most common subtype of ovarian cancer. It initially responds 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.

We use our in-house panel of chemotherapy and PARPi resistant HGSC cell lines and animal models to identify novel treatments for platinum-resistant ovarian cancer. The HGSC tumour matrix critically contributes to the development and maintenance of therapeutic resistance. We recently established decellularized HGSC tissue models so that we can explore tumour cell/matrix co-evolution with a view to identifying new matrix-directed anticancer therapies. To support clinical application of our discoveries we have pioneered a new bioinformatics pipeline known as LiquidCNA that can track the emergence of resistance in blood samples from ovarian cancer patients over time during therapy.

Evolution-based anti-cancer therapy

Adaptive Therapy is a novel treatment paradigm in which the drug dose is tailored to the evolution of chemotherapy resistance in individual patients over time. Prof Lockley and her team have demonstrated the feasibility and mechanistic basis of adaptive therapy in ovarian cancer and have successfully translated this approach to the ACTOv clinical trial (Adaptive ChemoTherapy in Ovarian cancer) that is currently recruiting patients from 10 UK hospital sites.

Rare gynaecological cancers

Prof Lockley has a special interest in rare gynaecological cancers, particularly ovarian germ cell tumours. She is Vice-Chair of the International Consortium of Malignant Germ Cell tumours (MaGIC), a global consortium of paediatric oncologists, gynaecologic oncologists, testicular cancer specialists, surgeons, pathologists, epidemiologists, statisticians, bioinformaticists, and biomedical scientists. Our mission is to advance germ cell cure through collaborative, multi-disciplinary research.

Tissue Collection

Prof Lockley set up and continues to lead the Barts Gynae Tissue Bank. This repository of blood, tissue and data kindly donated by Barts patients is widely used by scientists at the BCI and a range of industrial and academic collaborators. Since 2017, we have provided >1,000 samples, facilitating grant income (e.g. CRUK £5,000,000; European Research Council £2,000,000) and >20 academic publications.

Other Activities

• Research Culture and Environment Committee, Faculty of Medicine and Dentistry
• Postgraduate Tutor, Barts Cancer Institute
• Academic Advisor, Faculty of Medicine and Dentistry, QMUL
• Chief Investigator, Barts Gynae Tissue Bank
• Chief Investigator and Trial Management Group Chair, ACTOv clinical trial
• Trial Steering Group Chair, Dynamic Clinical Trial
• Panel member, Developmental Funding Pathway Scheme, Medical Research Council (MRC)
• MRC Clinical Trials Unit at UCL, Trial Steering Committee member
• Gynae Tumour Group, UK (formerly NCRI)
• Vice-Chair, Malignant Germ Cell Tumours International Consortium (MaGIC)

Major Funding

• 2025-2035 - Clinical Research Committee - Clinical Trial Award, “A phase II/III trial evaluating use of circulating serum miRNA as part of active surveillance for patients with stage I seminoma and dysgerminoma (OTIS-S)”. Co-Investigator. Lead Applicant Robert Huddart. £2.47M
• 2022-2027 - Anticancer Fund, RFA Evolutionary Therapy  “ACTOv: Adaptive Chemo-Therapy for Ovarian cancer”, €496,611. Principal Investigator
• 2022-2027 - Barts Charity Large Project Grant, “ACTOv Trial: Adaptive ChemoTherapy for Ovarian cancer”, £496,115.16. Principal Investigator
• 2023-2025 - CRUK Research Careers Committee, ‘Clinical Trial Fellowship’ CRUK, UCL Cancer Trials Centre, NIHR. Co-Investigator. Primary applicant: Dr Uma Mukerjee. £74,514.21
• 2018-2021- Barts Cancer Institute Incentivisation Fund, “Repurposing Fluticasone to improve platinum efficacy in high-grade serous) ovarian cancer” £190,000. Principal Investigator
• 2018-2020 - Industrial R&D grant: Academic collaboration with OCTIMET Oncology NV ‘Unravelling the mode of action of proprietary MET kinase inhibitors’. Co-applicant £443,531. Co-Applicant
• 2016-2021- Advanced CRUK Clinician Scientist Fellowship, "New treatments for chemotherapy-resistant high grade serous ovarian cancer” £1,177,994. Lead Applicant.
• 2014-2019- Barts and The London Charity Strategic Research Grant, “Discovering new therapies for chemotherapy resistant high grade serous ovarian cancer” £197,545
• 2011-2016- CRUK Clinician Scientist Fellowship, “Inflammatory Cytokines and Oncolytic Adenoviruses in Ovarian Cancer” £852,327

Recent Publications

Consensus and controversy in the management of paediatric and adult patients with ovarian immature teratoma: the Malignant Germ Cell International Consortium perspective Pashankar F, Murray MJ, Gell J et al. EClinicalMedicine (2024) (10) 102453

Identification, Monitoring and Reversibility of PARP Inhibitor Associated Clonal Haematopoiesis and Myelodysplastic Syndrome: A Case Series Musson EN, Lockley M, Mansour MR et al. Blood (2023) 142(10) 5607

Monitoring clone dynamics and reversibility in clonal haematopoiesis and myelodysplastic neoplasm associated with PARP inhibitor therapy—a role for early monitoring and intervention Nuttall Musson E, Miller RE, Mansour MR et al. Leukemia (2024) 38(10) 215-218

Seminoma and dysgerminoma: evidence for alignment of clinical trials and de-escalation of systemic chemotherapy Wood GE, Bunting CP, Veli M et al. Frontiers in Oncology 13(10) 1271647

Adolescent and Young Adult Germ Cell Tumors: Epidemiology, Genomics, Treatment, and Survivorship Travis LB, Feldman DR, Fung C et al. Journal of Clinical Oncology (2024) 42(10) 696-706

Author Correction: The copy number and mutational landscape of recurrent ovarian high-grade serous carcinoma Smith P, Bradley T, Gavarró LM et al. Nature Communications 14(10) 5992

Patient decision aids in mainstreaming genetic testing for women with ovarian cancer: A prospective cohort study Sobocan M, Chandrasekaran D, Sideris M et al. BJOG An International Journal of Obstetrics & Gynaecology (2024) 131(10) 848-857

The copy number and mutational landscape of recurrent ovarian high-grade serous carcinoma Smith P, Bradley T, Gavarró LM et al. Nature Communications 14(10) 4387

Extracellular matrix educates an immunoregulatory tumor macrophage phenotype found in ovarian cancer metastasis Puttock EH, Tyler EJ, Manni M et al. Nature Communications 14(10) 2514

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(10) 440-449

Team

Alison Berner: Clinical Lecturer

Mahrukh Heath: PhD student

Mohammed Ateeb Khan: Clinical research Training Fellow

Nikolina Bakali: PDRA, technician

Sophie Skingsley: PhD student

Biography

Academic positions

• 2022: Professor of Medical Oncology, Queen Mary University of London/UCLH
• 2016: Reader in Medical Oncology, Queen Mary University of London/UCLH
• 2016-2021: CRUK Advanced Clinician Scientist Fellowship
• 2015-2021: Deputy Centre Lead, Queen Mary University of London
• 2011-2016: CRUK Clinician Scientist Fellowship
• 2009-2011: HEFCE Senior Clinical Lecturer/Hon. Cons. Medical Oncology, Queen Mary University of London/Barts Health NHS Trust
• 2008-2009: NIHR Clinical Lecturer and Honorary Specialist Registrar in Oncology, University of Cambridge
• 2003-2007: MRC Clinical Research Training Fellow, Queen Mary University of London

Education and qualifications

• 2016: FRCP
• 2008: PhD (University of London)
• 2001: MRCP (Membership of the Royal College of Physicians), London
• 1997: MBBS (Bachelor of Medicine, Bachelor of Surgery), University College London, Distinctions in Medicine, Obstetrics/Gynaecology and Anatomy
• 1994: Honours Degree in Physiology, University College London, First Class