Dr Michelle Lockley

BSc, FRCP, PhD
Reader in Medical Oncology, Honorary Consultant
Deputy Centre Lead, Group Leader
Research Focus

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. We also use drug repurposing approaches to specifically target chemotherapy-resistant ovarian cancers and to improve the therapeutic benefit of oncolytic viral therapies.

Key Publications

Deconstruction of a Metastatic Tumor Microenvironment Reveals a Common Matrix Response in Human Cancers. Cancer Discov (2018) 8(3):304-319. PMID: 29196464

Beta3 integrin inhibition reduces the inflammatory toxicities induced by oncolytic adenovirus without compromising anticancer activity. Cancer Res (2015) 75(14):2811-21. PMID: 25977332

Chemotherapy Response Score (CRS): Development and validation of a system to quantify histopathological response to neoadjuvant chemotherapy in high-grade serous tubo-ovarian carcinoma. J Clin Oncol (2015) 33(22):2457-63. PMID: 26124480

Paclitaxel resistance increases oncolytic adenovirus efficacy via upregulated CAR expression and dysfunctional cell cycle control. Mol Oncol (2014) 9(4):791-805. PMID: 25560085

Major Funding
  • 2016-2020- Cancer Research UK, Advanced Clinician Scientist Fellowship: New treatments for chemotherapy-resistant high grade serous ovarian cancer, £1.178m
  • 2015-2019- Barts Charity, Strategic Research Grant: Discovering new therapies for chemotherapy resistant high grade serous ovarian cancer, £197,545
Other Activities
  • Academic Health Sciences Centre Committee
  • NCRI Early Onset Tumours Working Party
  • NCRI Gynaecological Cancers Clinical Study Group
  • NCRI Ovarian Cancer Subgroup
  • Member of the Malignant Germ Cell Tumours International Consortium (MaGIC)
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.

Circumventing resistance is therefore a major unmet clinical need. The Lockley lab has created a panel of chemotherapy resistant HGSC cell lines and are using these to identify novel treatments for chemoresistant disease.

Oncolytic viruses

We aim to improve the utility of oncolytic viruses, whose clinical potential has so far been limited by inflammatory toxicity induced when they are administered systemically.

We showed for the first time that these inflammatory toxicities can be reduced by inhibition of β3 integrin, a cell surface signalling and adhesion protein, without compromising anticancer activity.

We now aim to further improve viral anti-cancer efficacy through combination with immune-modulatory therapies.

Tissue Collection

I set up and continue 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 elsewhere. It is the basis of the ERC funded CanBuild project lead by Prof Balkwill, which is creating innovative and accurate 3D models of the human omentum in high grade serous cancer.

I am Medical Adviser for this project.

Other Activities
  • Academic Health Sciences Centre Committee
  • NCRI Early Onset Tumours Working Party
  • NCRI Gynaecological Cancers Clinical Study Group
  • NCRI Ovarian Cancer Subgroup
  • Barts Cancer Centre Executive Board
  • Barts Cancer CAG Research Governance Committee
  • eCancer Medicine online journal Editorial Board
  • Member of the Malignant Germ Cell Tumours International Consortium (MaGIC)
Major Funding
  • 2016-2020- Cancer Research UK, Advanced Clinician Scientist Fellowship: "New treatments for chemotherapy-resistant high grade serous ovarian cancer, £1.178m
  • 2015-2019- Barts Charity, Strategic Research Grant: Discovering new therapies for chemotherapy resistant high grade serous ovarian cancer, £197,545
  • 2011-2016- Cancer Research UK, Inflammatory Cytokines and Oncolytic Adenoviruses in Ovarian Cancer, £852,327
Recent Publications

Pathological chemotherapy response score is prognostic in tubo-ovarian high-grade serous carcinoma: A systematic review and meta-analysis of individual patient data Cohen PA, Powell A, Böhm S et al. Gynecologic Oncology (2019) (1)

A multicentre retrospective cohort study of ovarian germ cell tumours: Evidence for chemotherapy de-escalation and alignment of paediatric and adult practice. Newton C, Murali K, Ahmad A et al. Eur J Cancer (2019) 113(2) 19-27
https://www.ncbi.nlm.nih.gov/pubmed/30954883

Correction: Safety and utility of image-guided research biopsies in relapsed high-grade serous ovarian carcinoma-experience of the BriTROC consortium. Goranova T, Ennis D, Piskorz AM et al. Br J Cancer (2019) 120(2) 868
https://www.ncbi.nlm.nih.gov/pubmed/30862952

Mainstreamed genetic testing for women with ovarian cancer: first-year experience. Rahman B, Lanceley A, Kristeleit RS et al. J Med Genet (2019) 56(2) 195-198
https://www.ncbi.nlm.nih.gov/pubmed/29535157

Ovarian cancer in adolescents and young adults. Lockley M, Stoneham SJ, Olson TA Pediatr Blood Cancer (2019) 66(2) e27512
https://www.ncbi.nlm.nih.gov/pubmed/30350916

Histopathologic response to neoadjuvant chemotherapy as a prognostic biomarker in tubo-ovarian high-grade serous carcinoma: updated Chemotherapy Response Score (CRS) results. Böhm S, Le N, Lockley M et al. Int J Gynecol Cancer (2019) (2)
https://www.ncbi.nlm.nih.gov/pubmed/30683759

Copy number signatures and mutational processes in ovarian carcinoma. Macintyre G, Goranova TE, De Silva D et al. Nat Genet (2018) 50(2) 1262-1270
https://www.ncbi.nlm.nih.gov/pubmed/30104763

PHLDA1 Mediates Drug Resistance in Receptor Tyrosine Kinase-Driven Cancer. Fearon AE, Carter EP, Clayton NS et al. Cell Rep (2018) 22(2) 2469-2481
https://www.ncbi.nlm.nih.gov/pubmed/29490281

Deconstruction of a metastatic tumor microenvironment reveals a common matrix response in human cancers. Pearce OMT, Delaine-Smith R, Maniati E et al. Cancer Discov (2017) (1)
https://www.ncbi.nlm.nih.gov/pubmed/29196464

A comparison of p53 and WT1 immunohistochemical expression patterns in tubo-ovarian high-grade serous carcinoma before and after neoadjuvant chemotherapy. Casey L, Köbel M, Ganesan R et al. Histopathology (2017) 71(2) 736-742
https://www.ncbi.nlm.nih.gov/pubmed/28570008

For additional publications, please click here
Team

Postdoctoral Researchers in this group
Dr Joseph HoareDr Jayeta Saxena, Dr Vera Silva

Clinical Research Fellows
Dr Helen Hockings, Dr Georgina Wood

Laboratory Technician
Dr Francesco Nicolini

Biography

Academic positions

  • 2016: Reader in Medical Oncology, Queen Mary University of London/Barts Health NHS Trust/UCLH
  • 2015: CRUK Advanced Clinician Scientist Fellowship
    Senior Clinical Lecturer/Honorary Consultant in Medical Oncology, Deputy Centre Lead (2015), Queen Mary University of London/Barts Health NHS Trust/UCLH
  • 2011-2015: CRUK Clinician Scientist Fellowship, Queen Mary University of London/Barts Health NHS Trust
  • 2009-2011: HEFCE Senior Clinical Lecturer/Hon. Cons. Medical Oncology, Queen Mary University of London/Barts Health NHS Trust
  • 2008-2009: 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