Research

Pancreatic ductal adenocarcinoma (PDAC) has been deemed a ‘silent killer’, as it is asymptomatic at an early stage; more than 80% of patients therefore present with already disseminated disease, when curative surgery is not possible any more. Current treatments for such patients are largely inefficient, and their median survival is only 3-6 months. Overall five-year survival for pancreatic cancer patients is less than 5%.

We have therefore set ourselves a goal of making a difference for pancreatic cancer patients by developing a non-invasive test for early detection of PDAC.

This is based on a thorough understanding of developmental biology of this malignancy, stemming from analysis of the most common precursor lesions, PanINs, as a key source of potential early disease markers (PLOS One, 2013).

In addition, we performed an in-depth analysis of easily obtainable biofluid, urine (Proteom Clin Appl, 2008), and have recently described a panel of three protein biomarkers that can detect stage I-II PDAC with >90% accuracy (Clin Cancer Res, 2015).

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We have recently further validated this urinary biomarker panel in additional retrospectively collected samples, and developed a PancRISK score that enables us to stratify the patients into the ones with high or normal risk of developing pancreatic cancer. In addition, standardised LDT assays for the 3 biomarkers are currently being developed by 3rd Street Diagnostics, Cedars Sinai Medical Centre, LA and the affiliated CLIA/CAP ResearchDx laboratory at Irvine, CA. This is critical for evaluation of the biomarkers and PancRISK score further within a large prospective clinical study, UroPanc.  

In addition to proteins, we have also profiled miRNAs (Am J Cancer Res, 2015) and  volatile organic compounds in urine (Gastroenterology, 2018), and have recently started interrogating the utility of urinary ctDNA for mutation detection using ddPCR. Our final goal is to develop a highly accurate, multiomics-based ‘combo’, non-invasive test for early detection of pancreatic cancer.  This, we believe, will make a true impact on currently exceptionally poor prognosis of pancreatic cancer patients.

In addition to biomarker work, we are also interested in understanding the roles of two proteins, AGR2 and S100P (and its binding partner S100PBP), in pancreatic cancer. Both of these proteins are highly expressed in PanINs, primary PDACs and metastatic lesions, and also facilitate dissemination of pancreatic cancer cells both in vitro and in vivo (J Pathol 2003; Cancer Res, 2007; Cancer Res, 2011; Clin Exp Metastasis, 2013; Oncogene, 2017), and are therefore potentially promising therapeutic targets.

Finally, we have recently started studying EOPC – early onset pancreatic cancer, in order to decipher why this subgroup of patients is developing PDAC when they are around 20 years younger than the ‘classical’ PDAC patient population. Epidemiology and pathobiology of this poorly studied patient group is ongoing.

Patents

1. Patent Number: GB1501930.0: covers anti-SPAG1 antibody that was raised and validated in collaboration with CR-UK. It has now been commercialised by Cancer Research Technology Limited, UK.
2. A worldwide patent (WO2005062055A2 with Prof N. Lemoine) titled: “Methods for detecting neoplasia and markers thereof”. This patent is based on three proteins (S100P, AGR2 and SPAG1) that can aid diagnosis of pancreatic cancer in tissue biopsies/cytology material.
3. Patent (No 10001596.5 – 2404/ US 2013/0045884) with Dr C. Schroder and Prof J. Hoheisel, from University of Heidelberg, Germany: “Means and methods for diagnosing pancreatic cancer”. This patent is based on nconstruction and testing of the antibody array. Dr Schroder is now a CEO of spin out company Sciomics.
4. The PCT application “PCT/GB2016/050277: Biomarkers for pancreatic cancer” was published on 11th August 2016. In July 2017, the patent was filed within Europe and US and in additional 12 countries (Australia, Brazil, Canada, Chile, China, Israel, Japan, Europe, Korea, Mexico, New Zealand and Singapore).
5. ROC Patent I643869, 2018 on “The Preparation Methods of Molecularly Imprinted Materials” with Profs Hung-Yin Lin and Mei-Hwa Lee, National University of Kaohsiung (NUK), Kaohsiung, Taiwan. The patent is based on the construction of molecularly imprinted polymer for REG1 that will enable design of biosensor for detection of this protein in urine.

Other Activities

• STEM (Science, Technology, Engineering and Mathematics) Ambassador

Member of:

• Pathological Society of Great Britain and Ireland
• British and European Association of Cancer Research (BACR and EACR)
• American Association of Cancer Research (AACR)
• American Pancreatic Association (APA)
• EU Pancreas COST Action
• Pancreatic Cancer Europe

Major Funding

• 2019-2021- Barts Charity, Screening and Early Diagnosis (with S. Duffy N Lemoine, H Kocher), £1,5M
• 2019-2023-Pancreatic Cancer Research Fund, UroPanc trial, £1,59M
• 2018-2020- Cancer Research UK, Evaluation of Early Pancreatic Cancer Biomarkers in pre-diagnostic urine specimens, £235,000
• 2018-2020- Pancreatic Cancer Research Fund, KRAS Mutations in urinary cfDNA in pancreatic cancer patients, £95,704.69
• 2010-2016- CRUK (with N Lemoine and C Clhelala), Molecular Pathology and Genomics of pancreatic cancer: £1,2M
• 2009-2013- Pancreatic Cancer Research Fund, Non-invasive diagnosis of pancreatic Cancer, £280,000
• 2007-2012- Pancreatic Cancer Research Fund, A role of S100PBP in pancreatic cancer, £98,000

Recent Publications

A multilayered post-GWAS assessment on genetic susceptibility to pancreatic cancer López de Maturana E, Rodríguez JA, Alonso L et al. Genome Medicine (2021) 13(7)

Pentraxin 3 is a stromally-derived biomarker for detection of pancreatic ductal adenocarcinoma Goulart MR, Watt J, Siddiqui I et al. npj Precision Oncology (2021) 5(7)

From development to cancer - an ever-increasing role of AGR2. Jach D, Cheng Y, Prica F et al. American Journal of Cancer Research (2021) 11(1) 5249-5262
https://www.ncbi.nlm.nih.gov/pubmed/34873459

Gallbladder disease and pancreatic cancer risk: a multicentric case-control European study Rosato V, Gómez-Rubio P, Molina-Montes E et al. European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP) (2021) 30(7) 423-430

A 3-Dimensional Coculture Model to Visualize and Monitor Interaction Between Pancreatic Cancer and Islet β Cells Kumar S, Jach D, Macfarlane W et al. Pancreas (2021) 50(7) 982-989

Antibody Therapy Targeting Cancer-Specific Cell Surface Antigen AGR2 Y. Liu A, Crnogorac-Jurcevic T, J. Lai J et al. (2021) (10)

Leukocyte-DNA methylome explains a large proportion of the risk variability of pancreatic cancer De Maturana EL, Alonso L, Carrato A et al. Pancreatology (2021) 21(10) s13-s14

Non‐invasive biomarkers for earlier detection of pancreatic cancer—a comprehensive review Brezgyte G, Shah V, Jach D et al. Cancers (2021) 13(7)

Deciphering the complex interplay between pancreatic cancer, diabetes mellitus subtypes and obesity/BMI through causal inference and mediation analyses Molina-Montes E, Coscia C, Gómez-Rubio P et al. Gut (2021) 70(7) 319-329

A combination of urinary biomarker panel and PancRISK score for earlier detection of pancreatic cancer: A case-control study Debernardi S, O'Brien H, Algahmdi AS et al. PLoS Medicine (2020) 17(7)

Team

Postdoctoral Researchers
Dr Silvana Debernardi

Other members
Daria Jach, Greta Brezgyte

Biography

I obtained the MBBS degree and completed an MD thesis at the Medical Faculty, University of Zagreb in Croatia, and my PhD at the Imperial College School of Medicine in London. After a postdoctoral experience in molecular biology at CNRS in Toulouse, France and molecular oncology at CRUK laboratory at Hammersmith Hospital, London, I joined Barts Cancer Institute in November 2004.

In addition to research, my teaching responsibilities include Problem Based Learning (PBL) and Student Selective Component (SSC) for undergraduate students. I am Module Leader for Genomic Approaches to Cancer, a core module on the MSc/PGDip Cancer & Molecular Pathology and Genomics, MSc/PGDip Cancer & Molecular and Cellular Biology and MSc/PGDip Cancer & Therapeutics courses.

In 2006 I was awarded a Postgraduate Certificate in Academic Practice (PGCAP) and became a Fellow of the Higher Education Academy in 2009.