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

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)

Corrigendum to “Pathological chemotherapy response score is prognostic in tubo-ovarian high-grade serous carcinoma: A systematic review and meta-analysis of individual patient data” Gynecol. Oncol. 154 (2019) 441–448 (Gynecologic Oncology (2019) 154(2) (441–448), (S0090825819311813), (10.1016/j.ygyno.2019.04.679)) Cohen PA, Powell A, Böhm S et al. Gynecologic Oncology (2021) 161(7) 328-329

Objective responses to first-line neoadjuvant carboplatin–paclitaxel regimens for ovarian, fallopian tube, or primary peritoneal carcinoma (ICON8): post-hoc exploratory analysis of a randomised, phase 3 trial Morgan RD, McNeish IA, Cook AD et al. The Lancet Oncology (2021) 22(7) 277-288

Identification of a novel regulator of FANCD2 mediated DNA Repair Tse WY, Maniati E, Wang J et al. (2021) (10) 9200

The impact of a supranetwork multidisciplinary team (SMDT) on decision-making in testicular cancers: a 10-year overview of the Anglian Germ Cell Cancer Collaborative Group (AGCCCG) Shamash J, Ansell W, Alifrangis C et al. British Journal of Cancer (2021) 124(7) 368-374

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) (7)

Team

Postdoctoral Researchers in this group
Dr Joseph Hoare

Clinical Research Fellows
Dr Helen Hockings, Dr Georgina Wood

Laboratory Technician
Dr Francesco Nicolini

Biography

Academic positions