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
• Member of the Malignant Germ Cell Tumours International Consortium (MaGIC)

Major Funding

• 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

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)

Surgical management and outcomes for stage 1 malignant ovarian germ cell tumours: A UK multicentre retrospective cohort study Graham R, MacDonald ND, Lockley M et al. European Journal of Obstetrics and Gynecology and Reproductive Biology (2022) 271(7) 138-144

Single-agent carboplatin AUC10 in metastatic seminoma: A multi-centre UK study of 216 patients Alifrangis C, Sharma A, Chowdhury S et al. European Journal of Cancer (2022) 164(7) 105-113

Venous thromboembolism in women with ovarian cancer undergoing neoadjuvant chemotherapy prior to cytoreductive surgery: A retrospective study Oxley SG, Achampong YA, Sambandan N et al. Acta Obstetricia et Gynecologica Scandinavica (2021) 100(7) 2091-2096

423 Results of the avoiding late diagnosis of ovarian cancer (ALDO) project; a pilot national surveillance program for BRCA mutation-carriers Philpott S, Raikou M, Manchanda R et al. International Journal of Gynecological Cancer (2021) 31(10) a373-a374

Implementation of multigene germline and parallel somatic genetic testing in epithelial ovarian cancer: Signpost study Chandrasekaran D, Sobocan M, Blyuss O et al. Cancers (2021) 13(7)

LiquidCNA: Tracking subclonal evolution from longitudinal liquid biopsies using somatic copy number alterations Lakatos E, Hockings H, Mossner M et al. iScience (2021) 24(7)

Re: ‘Can we replace adjuvant chemotherapy with surveillance for stage IA-C immature ovarian teratomas of any grade? An international multicenter analysis’ Lockley M, Stoneham S, Shamash J et al. European Journal of Cancer (2021) 152(7) 255-256

A human multi-cellular model shows how platelets drive production of diseased extracellular matrix and tissue invasion Malacrida B, Nichols S, Maniati E et al. iScience (2021) 24(7)

Chloroxine overrides DNA damage tolerance to restore platinum sensitivity in high-grade serous ovarian cancer Silva VL, Saxena J, Nicolini F et al. Cell Death and Disease (2021) 12(7)

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