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

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 Dis (2021) 12(2) 395
https://www.ncbi.nlm.nih.gov/pubmed/33854036

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. Lancet Oncol (2021) 22(2) 277-288
https://www.ncbi.nlm.nih.gov/pubmed/33357510

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. Br J Cancer (2021) 124(2) 368-374
https://www.ncbi.nlm.nih.gov/pubmed/32989229

Single-agent carboplatin AUC10 in metastatic seminoma: A multi-centre UK study of 216 patients. Alifrangis C, Sharma A, Chowdhury S et al. Eur J Cancer (2020) (2)
https://www.ncbi.nlm.nih.gov/pubmed/33041185

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 (2020) 157(7) 558-559

Response to: A multicentre retrospective cohort study of ovarian germ cell tumours: Evidence for chemotherapy de-escalation and alignment of paediatric and adult practice. Berney DM, Shamash J, Stoneham S et al. Eur J Cancer (2020) 130(2) 267-268
https://www.ncbi.nlm.nih.gov/pubmed/32199694

Role of Ki67 Proliferation Index and CD8 Tumour-Infitrating Lymphocyte Counts in Predicting Outcome in High-Grade Serous Tubo-Ovarian Carcinoma (HGSC) Showing No/Partial Response to Neoadjuvant Chemotherapy Casey L, Powell A, Bohm S et al. MODERN PATHOLOGY (2020) 33(11) 1024-1024
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000518328902210&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=612ae0d773dcbdba3046f6df545e9f6a

Mainstreamed genetic testing in ovarian cancer: patient experience of the testing process. McLeavy L, Rahman B, Kristeleit R et al. Int J Gynecol Cancer (2020) 30(2) 221-226
https://www.ncbi.nlm.nih.gov/pubmed/31744886

Ovarian germ cell tumour classification: views from the testis. Berney DM, Stoneham S, Arora R et al. Histopathology (2020) 76(2) 25-36
https://www.ncbi.nlm.nih.gov/pubmed/31846529

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