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. 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.

Tissue Collection

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.

Other Activities

• BCI Tissue Bank academic lead
• Postgraduate Tutor
• NCRI Early Onset Tumours Working Party
• NCRI Gynaecological Cancers Clinical Study Group
• NCRI Ovarian Cancer Subgroup
• Barts Cancer Centre Executive Board
• Vice-Chair of the Malignant Germ Cell Tumours International Consortium (MaGIC)

Major Funding

• 2022-2027 - Anticancer Fund, RFA Evolutionary Therapy (2021-2027) “ACTOv: Adaptive ChemoTherapy for Ovarian cancer”, €496,611
• 2021-2024 - Barts Charity Large Project Grant, “ACTOv Trial: Adaptive ChemoTherapy for Ovarian cancer”, £496,115.16
• 2018-2021- Barts Cancer Institute Incentivisation Fund, “Repurposing Fluticasone to improve platinum efficacy in (high-grade serous) ovarian cancer” £190,000
• 2016-2021- Advanced CRUK Clinician Scientist Fellowship, "New treatments for chemotherapy-resistant high grade serous ovarian cancer” £1,177,994
• 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

Biography

Academic positions

• 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
• 2007: 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