Innovation

Research topic

Integration of patient clinical management with cutting edge research to improve the diagnosis and treatment of ovarian cancer

The importance of this research

Ovarian cancer is the leading cause of death from gynaecological malignancy in the western world. Worldwide there are more than 225,000 new cases of ovarian cancer and 140,000 deaths each year. Ireland has one of the highest mortality rates in Europe from ovarian cancer, with over 350 women diagnosed annually, and 65% dying within 5 years of diagnosis. Ovarian cancer has remained the most challenging of all the gynaecological malignancies for two reasons. First, early-stage disease while having a good prognosis, cannot be detected easily as it is either asymptomatic or the symptoms are non-specific. Second, standard chemotherapy approaches such as paclitaxel and carboplatin often fail and patients develop recurrent chemoresistant disease.

In 2014, internationally recognised ovarian cancer clinical and scientific experts across Ireland came together to address the clinical challenges posed by ovarian cancer. INNOVATION-the Irish National Network for Ovarian Cancer Collaboration was established with a mission to integrate patient clinical pathways with cutting edge research to improve diagnosis and treatment of ovarian cancer.

The consortium agreed to implement comprehensive longitudinal monitoring of all ovarian cancer patients in Ireland, with biobanking of tissue samples for detailed molecular interrogation of tumour evolution. The advanced analysis of ovarian cancer epidemiology, genomic characterisations and clinical observations could lead to the development of novel therapeutic targets as well as make an impact on mortality of ovarian cancer and the cost effectiveness of treatment. This INNOVATION strategy will provide a paradigm for how a significant healthcare and economic impact could be made for other more prevalent tumours.

Team

INNOVATION comprises internationally recognised ovarian cancer clinical and scientific experts.

Individuals

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Organisations

Molecular Medicine Ireland
Irish Gynaecology Oncology Nurses Group (IGONG)
Ovacare
SOCK
Emer Casey Foundation
Irish Cancer Society

Abbreviations

CWIUH (Coombe Womens and Infants University Hospital)
MMUH (Mater Misericordiae University Hospital)
NIBRT (National Institute for Bioprocessing Research and Training)
RCSI (Royal College of Surgeons in Ireland)
SJH (St. James’s Hospital)
TCD (Trinity College Dublin)

About the Consortium

INNOVATION comprises internationally recognised ovarian cancer clinical and scientific experts. The consortium was established in 2014 to address the dreadful mortality associated with ovarian cancer. The mission of the consortium is to integrate patient clinical pathways with cutting edge research to improve diagnosis and treatment of ovarian cancer. The group aims to secure funding to create a national centre of excellence for ovarian cancer and has identified key priority research areas that have the potential to improve outcomes for ovarian cancer patients. The group intend to implement comprehensive longitudinal monitoring of all ovarian cancer patients in Ireland, with biobanking of tissue/blood samples for detailed molecular interrogation of tumour evolution. This will form the backbone for the various technologies to be applied.

The consortium cover a range of expertise integral to ovarian cancer clinical management and research including;

• Medical oncologists
• Gynaecological oncologists
• Radiologists
• Pathologists
• Geneticists
• Scientists with expertise in genomics, proteomics, glycosylation, epigenetics
• Molecular Biologists
• Biochemists
• Cell biologists
• Stem cell biologists
• Microbiologists specialising in cancer therapy using microbes
• Medical Ethics experts
• Mathematical modellers
• Pharmacoepidemiologists
• Bioinformaticians
• Clinical nurse specialists
• Patient advocacy groups and charities

Collaborative Funding to date

Many members of the group have been collaborating prior to the formal establishment of INNOVATION and have secured funding from the Health Research Board, Science Foundation Ireland, the Royal City of Dublin Hospital Trust, the Emer Casey Foundation, SOCK and Fujirebio Diagnostics. Examples of recent projects include;

• What is the circulating tumour cell and the role of the immune editing in the metastatic cascade?
• Oncology 1 strand of the Biomedical Diagnostics Institute - Dublin City University
• A risk model for prediction of venous thromboembolism in gynaecological cancer patients post surgery
• Interrogation of the onco-metabolome in ovarian cancer
• Evaluation of the half life of HE4 in optimally debulked epithelial ovarian cancer patients
• A therapeutic roadmap for ovarian cancer using MyD88 and MAD2 as prognostic indicators
• Epigenetic regulation of glycosylation and the impact on chemoresistance in cancer

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Recent Publications since 2015

Stanicka J, Rieger L, O'Shea S, Cox O, Coleman M, O'Flanagan C, Addario B, McCabe N, Kennedy R, O'Connor R. FES-related tyrosine kinase activates the insulin-like growth factor-1 receptor at sites of cell adhesion. Oncogene. 2018 Mar 15. doi: 10.1038/s41388-017-0113-z. [Epub ahead of print] PubMed PMID:29540831.

Byrne T, Nelson L, Beirne JP, Sharpe D, Quinn JE, McCluggage WG, Robson T, Furlong F. BRCA1 and MAD2 Are Coexpressed and Are Prognostic Indicators in Tubo-ovarian High-Grade Serous Carcinoma. Int J Gynecol Cancer. 2018 Mar;28(3):472-478. doi: 10.1097/IGC.0000000000001214. PubMed PMID: 29465507.

Annett S, Robson T. Targeting cancer stem cells in the clinic: Current status and perspectives. Pharmacol Ther. 2018 Feb 5. pii: S0163-7258(18)30020-2. doi:10.1016/j.pharmthera.2018.02.001. [Epub ahead of print] Review. PubMed PMID:29421575.

McCluggage WG, Irving JA, Chong AS, Clarke BA, Young RH, Foulkes WD, Rivera B. Ovarian Microcystic Stromal Tumors Are Characterized by Alterations in the Beta-Catenin-APC Pathway and May be an Extracolonic Manifestation of Familial Adenomatous Polyposis. Am J Surg Pathol. 2018 Jan;42(1):137-139. doi: 10.1097/PAS.0000000000000981. PubMed PMID: 29076875.

Thompson C, McCormick C, Kamran W, O'Riain C, Norris L, Gallagher D, Gleeson N. Risk reduction surgery (RRS) for tubo-ovarian cancer in an Irish gynaecological practice: an analysis of indications and outcomes. Ir J Med Sci.2018 Jan 3. doi: 10.1007/s11845-017-1717-6. [Epub ahead of print] PubMed PMID:29299762.

Arts FA, Keogh L, Smyth P, O'Toole S, Ta R, Gleeson N, O’Leary JJ, Flavin R, Sheils O. miR-223 potentially targets SWI/SNF complex protein SMARCD1 in atypical proliferative serous tumor and high-grade ovarian serous carcinoma. Hum Pathol. 2017 Dec;70:98-104. doi: 10.1016/j.humpath.2017.10.008. Epub 2017 Oct 24. PubMed  PMID: 29079174.

McGivern N, El-Helali A, Mullan P, McNeish IA, Paul Harkin D, Kennedy RD, McCabe N. Activation of MAPK signalling results in resistance to saracatinib (AZD0530) in ovarian cancer. Oncotarget. 2017 Dec 20;9(4):4722-4736. doi: 10.18632/oncotarget.23524. eCollection 2018 Jan 12. PubMed PMID: 29435137; PubMed Central PMCID: PMC5797008.

Vermeulen CKM, Tadesse W, Timmermans M, Kruitwagen RFPM, Walsh T. Only complete tumour resection after neoadjuvant chemotherapy offers benefit over suboptimal debulking in advanced ovarian cancer. Eur J Obstet Gynecol Reprod Biol. 2017 Dec;219:100-105. doi: 10.1016/j.ejogrb.2017.10.019. Epub 2017 Oct 19. PubMed PMID: 29078115.

Sulaiman G, Cooke A, Ffrench B, Gasch C, Abdullai OA, O'Connor K, Elbaruni S,  Blackshields G, Spillane C, Keegan H, McEneaney V, Knittel R, Rogers A, Jeffery IB, Doyle B, Bates M, d'Adhemar C, Lee MY, Campbell EL, Moynagh PN, Higgins DG, O'Toole S, O'Neill L, O’Leary JJ, Gallagher MF. MyD88 is an essential component of retinoic acid-induced differentiation in human pluripotent embryonal carcinoma cells. Cell Death Differ. 2017 Nov;24(11):1975-1986. doi: 10.1038/cdd.2017.124. Epub 2017 Sep 8. PubMed PMID: 28885616; PubMed Central PMCID: PMC5635222.

Singh N, Faruqi A, Kommoss F, McCluggage WG, Trevisan G, Senz J, Lum A, Gilks CB, Anglesio M. Extrauterine high-grade serous carcinomas with bilateral adnexal involvement as the only two disease sites are clonal based on tp53 sequencing results: implications for biology, classification, and staging. Mod Pathol. 2017 Nov 17. doi: 10.1038/modpathol.2017.159. [Epub ahead of print] PubMed PMID: 29148539.

Taylor J, McCluggage WG. Ovarian Sex Cord-stromal Tumors With Melanin Pigment: Report of a Previously Undescribed Phenomenon. Int J Gynecol Pathol. 2017 Nov 14. doi: 10.1097/PGP.0000000000000471. [Epub ahead of print] PubMed PMID: 29140884.

Ffrench B, Gasch C, Hokamp K, Spillane C, Blackshields G, Mahgoub TM, Bates M, Kehoe L, Mooney A, Doyle R, Doyle B, O'Donnell D, Gleeson N, Hennessy BT, Stordal B, O'Riain C, Lambkin H, O'Toole S, O’Leary JJ, Gallagher MF. CD10(-)/ALDH(-) cells are the sole cisplatin-resistant component of a novel ovarian cancer stem cell hierarchy. Cell Death Dis. 2017 Oct 19;8(10):e3128. doi: 10.1038/cddis.2017.379. PubMed PMID: 29048400; PubMed Central PMCID: PMC5680566.

Duffy MJ, Synnott NC, Crown J. Mutant p53 as a target for cancer treatment. Eur J Cancer. 2017 Sep;83:258-265. doi: 10.1016/j.ejca.2017.06.023. Epub 2017 Jul 28. Review. PubMed PMID: 28756138.

Singh N, Benson JL, Gan C, Anglesio M, Arora R, Faruqi AZ, Hirschowitz L, Kommoss F, Scott K, Trevisan G, Leen SLS, Wilkinson N, Gilks CB, McCluggage WG. Disease Distribution in Low-stage Tubo-ovarian High-grade Serous Carcinoma (HGSC): Implications for Assigning Primary Site and FIGO Stage. Int J Gynecol Pathol. 2017 Aug 4. doi: 10.1097/PGP.0000000000000429. [Epub ahead of print] PubMed PMID: 28787323.

To EE, Vlahos R, Luong R, Halls ML, Reading PC, King PT, Chan C, Drummond GR,  Sobey CG, Broughton BRS, Starkey MR, van der Sluis R, Lewin SR, Bozinovski S, O'Neill LAJ, Quach T, Porter CJH, Brooks DA, O’Leary JJ, Selemidis S. Endosomal NOX2 oxidase exacerbates virus pathogenicity and is a target for antiviral therapy. Nat Commun. 2017 Jul 12;8(1):69. doi: 10.1038/s41467-017-00057-x. PubMed PMID: 28701733; PubMed Central PMCID: PMC5507984.

Byrne T, Coleman HG, Cooper JA, McCluggage WG, McCann A, Furlong F. The association between MAD2 and prognosis in cancer: a systematic review and meta-analyses. Oncotarget. 2017 Jun 8;8(60):102223-102234. doi: 10.18632/oncotarget.18414. eCollection 2017 Nov 24. PubMed PMID: 29254238; PubMed Central PMCID: PMC5731948.

Wong LFA, Anglim B, Wahab NA, Gleeson N. A review of the open laparoscopic Hasson technique and retrieval of adnexal specimen via umbilicus. J Obstet Gynaecol. 2017 May;37(4):487-491. doi: 10.1080/01443615.2016.1269226. Epub 2017 Feb 17. PubMed PMID: 28421907.

Karam A, Ledermann JA, Kim JW, Sehouli J, Lu K, Gourley C, Katsumata N, Burger RA, Nam BH, Bacon M, Ng C, Pfisterer J, Bekkers RLM, Casado Herráez A, Redondo A, Fujiwara H, Gleeson N, Rosengarten O, Scambia G, Zhu J, Okamoto A, Stuart G, Ochiai K; participants of the 5th Ovarian Cancer Consensus Conference. Fifth Ovarian Cancer Consensus Conference of the Gynecologic Cancer InterGroup: first-line interventions. Ann Oncol. 2017 Apr 1;28(4):711-717. doi: 10.1093/annonc/mdx011. PubMed PMID: 28327917.

Gasch C, Ffrench B, O’Leary JJ, Gallagher MF. Catching moving targets: cancer stem cell hierarchies, therapy-resistance & considerations for clinical intervention. Mol Cancer. 2017 Feb 23;16(1):43. doi: 10.1186/s12943-017-0601-3. Review. PubMed PMID: 28228161; PubMed Central PMCID: PMC5322629.

Fernández ML, DiMattia GE, Dawson A, Bamford S, Anderson S, Hennessy BT, Anglesio MS, Shepherd TG, Salamanca C, Hoenisch J, Tinker A, Huntsman DG, Carey MS. Differences in MEK inhibitor efficacy in molecularly characterized low-grade serous ovarian cancer cell lines. Am J Cancer Res. 2016 Oct 1;6(10):2235-2251. eCollection 2016. PubMed PMID: 27822414; PubMed Central PMCID: PMC5088288.

Martin F, Long JC, O'Toole SA, O’Leary JJ, Abu Saadeh F, Gleeson N, Norris LA. PO-14 - Tumour expression of coagulation proteases of the aPC pathway – a role in the pathogenesis of gynaecological cancers? Thromb Res. 2016 Apr;140 Suppl 1:S181. doi: 10.1016/S0049-3848(16)30147-5. Epub 2016 Apr 8. PubMed PMID: 27161702.

Parkes EE, Kennedy RD. Clinical Application of Poly(ADP-Ribose) Polymerase Inhibitors in High-Grade Serous Ovarian Cancer. Oncologist. 2016 May;21(5):586-93. doi: 10.1634/theoncologist.2015-0438. Epub 2016 Mar 28. Review. PubMed PMID: 27022037; PubMed Central PMCID: PMC4861365.

McCabe N, Kennedy RD, Prise KM. The role of PTEN as a cancer biomarker. Oncoscience. 2016 Mar 3;3(2):54-5. eCollection 2016. PubMed PMID: 27014722; PubMed Central PMCID: PMC4789570.

Harter P, Johnson T, Berton-Rigaud D, Park SY, Friedlander M, Del Campo JM, Shimada M, Forget F, Mirza MR, Colombo N, Zamagni C, Chan JK, Imhof M, Herzog TJ, O'Donnell D, Heitz F, King K, Stinnett S, Barrett C, Jobanputra M, Xu CF, du Bois A. BRCA1/2 mutations associated with progression-free survival in ovarian cancer patients in the AGO-OVAR 16 study. Gynecol Oncol. 2016 Mar;140(3):443-9. doi:10.1016/j.ygyno.2015.12.027. Epub 2015 Dec 29. PubMed PMID: 26740259.

Lawler M, Gavin A, Salto-Tellez M, Kennedy RD, Van Schaeybroeck S, Wilson RH, Harkin DP, Grayson M, Boyd RE, Hamilton PW, McArt DG, James J, Robson T, Ladner RD, Prise KM, O'Sullivan JM, Harrison T, Murray L, Johnston PG, Waugh DJ.Delivering a research-enabled multistakeholder partnership for enhanced patient care at a population level: The Northern Ireland Comprehensive Cancer Program. Cancer. 2016 Mar 1;122(5):664-73. doi: 10.1002/cncr.29814. Epub 2015 Dec 22. PubMed PMID: 26695702; PubMed Central PMCID: PMC4864440.

Baird R, Banks I, Cameron D, Chester J, Earl H, Flannagan M, Januszewski A, Kennedy R, Payne S, Samuel E, Taylor H, Agarwal R, Ahmed S, Archer C, Board R, Carser J, Copson E, Cunningham D, Coleman R, Dangoor A, Dark G, Eccles D, Gallagher C, Glaser A, Griffiths R, Hall G, Hall M, Harari D, Hawkins M, Hill M, Johnson P, Jones A, Kalsi T, Karapanagiotou E, Kemp Z, Mansi J, Marshall E, Mitchell A, Moe M, Michie C, Neal R, Newsom-Davis T, Norton A, Osborne R, Patel G, Radford J, Ring A, Shaw E, Skinner R, Stark D, Turnbull S, Velikova G, White J, Young A, Joffe J, Selby P. An Association of Cancer Physicians' strategy for improving services and outcomes for cancer patients. Ecancermedicalscience. 2016 Jan 5;10:608. doi: 10.3332/ecancer.2016.608. eCollection 2016. PubMed PMID: 26913066; PubMed Central PMCID: PMC4762575.

Sölétormos G, Duffy MJ, Othman Abu Hassan S, Verheijen RH, Tholander B, Bast RC Jr, Gaarenstroom KN, Sturgeon CM, Bonfrer JM, Petersen PH, Troonen H, CarloTorre G, Kanty Kulpa J, Tuxen MK, Molina R. Clinical Use of Cancer Biomarkers in Epithelial Ovarian Cancer: Updated Guidelines From the European Group on Tumor Markers. Int J Gynecol Cancer. 2016 Jan;26(1):43-51. doi: 10.1097/IGC.0000000000000586. PubMed PMID: 26588231; PubMed Central PMCID:
PMC4679342.

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Collaborators

International Consortia
All Ireland cooperative oncology research group- ICORG
Centre for Cancer Research & Cell Biology, Queens University, Belfast.
The European Network of Translational Research in Gynaecological Oncology (ENTRIGO)

Individuals

Prof. Gordon Mills, MD Anderson, Texas, USA.
Dr. Maurie Markman, Cancer Treatment Centers of America.
Prof Linda Sharp, University of Newcastle, UK
Prof Lance Liotta, George Mason University, USA
Prof Chip Petricoin, George Mason University, USA
Dr Britta Stordal, Middlesex University, UK

Industry

Abbott Laboratories
Adnagen AG
Affymetrix Inc.
Agilent Technologies
Almac Group Ltd.
Cellix Ltd.
Fujirebio Diagnostics Inc.
GE Healthcare
Genentech Inc. (Roche)
Greiner Bio-one Inc.
GlaxoSmithKline Plc.
Illumina Inc.
Johnson and Johnson
Leo Laboratories Ltd.
Life Technologies Inc.
Lonza Group
Myriad
Novartis AG
Oncomark Ltd.
Opsona Therapeutics Ltd.
Qiagen Ltd.
Raman Diagnostics Ltd.
Randox Laboratories Ltd.
Roche
ScreenCell

For further information please contact: Sharon O'Toole
Email: shotoole@tcd.ie

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