Professor Michelle Lockley
Group Leader
Clinical Professor of Medical Oncology, Honorary Consultant
Overview
Our lab aims to improve treatments for women with ovarian cancer. We are interested in understanding how cancer cells and their tumour microenvironment co-evolve during drug therapy, which usually results in treatment resistance. We use this information to develop new drug dosing regimens and combinations to constrain this evolution. Our goal is to develop personalised therapeutic regimens that respond to the evolutionary dynamics in individual patients in order to preserve drug sensitivity and prolong progression free survival. One such strategy is Adaptive Therapy, which we have developed from proof-of-concept in ovarian cancer and are now testing in a multicentred, randomised clinical trial.
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.
Key Publications
Adaptive Therapy Exploits Fitness Deficits in Chemotherapy‑Resistant Ovarian Cancer to Achieve Long‑Term Tumor Control. Cancer Res (2025) [Epub ahead of print]. PMID: 40299825
Study protocol for Adaptive ChemoTherapy for Ovarian cancer (ACTOv): a multicentre phase II randomised controlled trial to evaluate the efficacy of adaptive therapy (AT) with carboplatin, based on changes in CA125, in patients with relapsed platinum‑sensitive high‑grade serous or high‑grade endometrioid ovarian cancer. BMJ Open (2024) 14(12):e091262. PMID: 39806715
A novel cell line panel reveals non‑genetic mediators of platinum resistance and phenotypic diversity in high‑grade serous ovarian cancer. Gynecol Oncol (2022) 167(1):96‑106. PMID: 35918200
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 Dis (2021) 12(4):395. PMID: 33854036
See recent publicationsMajor Funding
- 2026-2032: Cancer Research UK, Discovery Research Committee – Programme Foundation Award, “Targeting the evolution of drug resistance in high-grade serous ovarian cancer” £1,489,394. Principal Investigator
- 2025-2035: Cancer Research UK 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
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)
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
Related News
Smarter chemotherapy approach could delay drug resistance in ovarian cancer
Adaptive chemotherapy can prolong survival in lab models of ovarian cancer, according to new results. The findings could pave the way for a more effective and gentler approach to treating ovarian cancer that uses existing drugs in a more intelligent way.
General News 30 April 2025
Clinical study to investigate new personalised treatment for ovarian cancer
Dr Michelle Lockley from Barts Cancer Institute at Queen Mary University of London has received funding from Barts Charity and the Anticancer Fund to investigate a new personalised treatment approach for ovarian cancer that has returned after previous chemotherapy.
General News 14 March 2022
Ovarian Cancer Perspectives: Q&A with Dr Michelle Lockley
In recognition of Ovarian Cancer Awareness Month, we spoke with Dr Michelle Lockley, Group Leader and clinical researcher in BCI’s Centre for Cancer Cell and Molecular Biology. Dr Lockley’s research group focuses on improving treatments for women with ovarian cancer, particularly for those whose tumours are resistant to chemotherapy.
General News 18 March 2021