P04. Imperial College of Science, Technology and Medicine,
London, United Kingdom
Principal Investigator: Hani Gabra

Brief description of the organisation and summary of experience relevant to the project
IC’s West London Gynaecological Cancer Centre at Queen Charlotte’s and Hammersmith Hospital is responsible for the care of all ovarian cancer patients in West London, undertaking primary surgery for around 130 newly diagnosed ovarian cancers per annum as well as treating around 80 patients with recurrent ovarian cancer annually. Closely linked to this is the Ovarian Cancer Action (OCA) Research Centre with over 40 ovarian cancer scientists. We have constructed a frozen tumour bank of over 450 ovarian cancers with over 200 associated blood and urine samples. This has led to Affymetrix expression array and SNP chip array as well as reverse phase protein array and MIP array and metabonomic profiling on 165 patients and g-PET and RNA-Seq on a smaller number of patients. Our bioinformatics team is focussed on exploring cross platform OMICS using these data sets. The OCA Research Centre also has separate research groups in ovarian cancer tumour suppressor genes, ovarian cancer stem cell biology, molecular basis of platinum resistance, epigenetics of ovarian cancer, ovarian cancer immunotherapy, ovarian cancer target discovery, and an active phase I-III clinical trials group.
IC’s Division of Cancer houses more than 250 researchers constituting the recently formed CR-UK Imperial Cancer Research Centre. We have direct access to next generation sequencing, expression array, SNP array, TMA generation and the most extensive preclinical and clinical molecular imaging facilities in Europe with 3 cyclotrons and 3 separate research imaging centres (MRC, CR-UK and GSK) on site.

Main tasks attributed in the project
P4 participates in WP2, WP3, WP5 and WP6. It will contribute both retrospectively and prospectively collected samples. P4 will investigate candidate biomarkers associated with platinum resistance in WP3. The bioinformatics team will integrate with WP5 to explore cross platform OMICS development across the OCTIPS. We will utilise samples from a clinical trial in WP6 to further validate predictive biomarker candidates and contribute to expand the infrastructure for future studies using the data generated in OCTIPS.

Short profile of staff members
Hani Gabra, Ph.D., FRCP, is an internationally recognised ovarian cancer clinician scientist. He is Lead Clinician for Gynaecological Cancer at Imperial, Head of the Section of Molecular Therapeutics within the Division of Cancer and Director of the Ovarian Cancer Action Research Centre. He has secured over £20M of peer-reviewed competitively acquired grants in total with over £2M research income. His groups are focused on the identification and clinical development of tumour suppressor genes WWOX and OPCML, and in the molecular basis of ovarian cancer treatment failure. He led the SCOTROC group’s ovarian cancer section for 5 years and is a member of the National Cancer Research Institute (NCRI) Ovarian Cancer Subgroup. He is founding president of the European Translational Research Network for Ovarian Cancer (EUTROC).
Euan Stronach, Ph.D., is Group Leader for the ovarian cancer molecular therapeutics lab. His group identified many of the targets associated with platinum resistance (HDAC4, STAT1, AKT, FOLR2, DNA-PK) and his laboratory houses extensive biological resources associated with the Edinburgh cell lines described extensively in this application. His group houses strong skills in bioinformatics and functional validation of targets for therapy that are crucial to this application. He has contributed to translational research in many of the Scottish group studies and is conducting translational research within the AKT inhibitor trial in WP6.

1. Perumal M, Stronach EA, Gabra H, Aboagye EO. Evaluation of 2-Deoxy-2-[(18)F]Fluoro-D-glucose- and 3'-Deoxy-3'-[(18)F]Fluorothymidine-Positron Emission Tomography as Biomarkers of Therapy Response in Platinum-Resistant Ovarian Cancer. Mol Imaging Biol. doi:10.1007/s11307-012-0554-2, 2012.
2. McKie AB, et al. Gabra H. The OPCML Tumor Suppressor Functions as a Cell Surface Repressor-Adaptor, Negatively Regulating Receptor Tyrosine Kinases in Epithelial Ovarian Cancer. Cancer Discov 2:156-171, 2012.
3. Stronach EA. et al, Gabra, H. HDAC4-Regulated STAT1 Activation Mediates Platinum Resistance in Ovarian Cancer. Cancer Res. 71:4412-4422, 2011.
4. Stronach EA, Chen M, Maginn EN, Agarwal R, Mills GB, Wasan H, Gabra H. DNA-PK Mediates AKT Activation and Apoptosis Inhibition in Clinically AcquiredPlatinum Resistance. Neoplasia 13, 1069-1108, 2011.
5. Stronach EA, Cheraghchi-Bashi A, Chen M, Gabra, H. in Emerging Therapeutic Targets in Ovarian Cancer Vol. 1  (eds SB Kaye, R Brown, H Gabra, & M Gore) Ch. 4, 73-94, Springer, 2011.
6. Gabra H. Back to the future: Targeting molecular changes for platinum resistance reversal. Gynecol Oncol. 118:210-1, 2010.
7. Sellar GC, Watt KP, Rabiasz GJ, Stronach EA, Li L, Miller EP, Massie CE, Miller J, Contreras-Moreira B, Scott D, Brown I, Williams AR, Bates PA, Smyth JF, Gabra H. OPCML at 11q25 is epigenetically inactivated and has tumor-suppressor function in epithelial ovarian cancer. Nat Genet. 34:337-43, 2003.