The Avner Australian Pancreatic Cancer Matrix Atlas (APMA) is a national and international portal for pancreatic cancer and matrix biology research.
The Avner Australian Pancreatic Cancer Matrix Atlas (APMA) is a national and international portal for pancreatic cancer and matrix biology research. Desmoplasia (fibrosis) is a key hallmark of pancreatic cancer, which can be targeted in concert with tumour cell-centric therapies. The overarching goal of APMA is to facilitate the translation of stromal-centric therapy as a mainstay in our emerging multimodal armoury against pancreatic cancer. We have a number of ongoing extracellular matrix (ECM) drug targeting programs where we can rapidly test matrix manipulations from this resource (with or without) standard-of-care chemotherapy.
Using novel tissue analysis and decellularisation techniques, we map the distribution, organisation, and assembly of fibrotic stroma in human pancreatic cancer and matched non-malignant adjacent tissue to identify new ECM targets specific to pancreatic cancer progression.
Samples are collected fresh from surgery from tumour regions and matched non-malignant adjacent fibrotic tissue for each patient. Each tissue sample is split into multiple parts and bio-banked as either: i) fresh frozen, ii) frozen OCT embedded, iii) formalin fixed, paraffin embedded, iv) xenografted orthotopically or subcutaneously in immunocompromised mice, or v) entered immediately into our up-and-running decellularisation pipeline (Figure 1). Specimens are then fully annotated and subsequently sequenced. Notably, we are the first team to have optimised an innovative decellularisation approach for the assessment of matrisomal proteins in human pancreatic tissue specimens. This comprehensive biobanking methodology aligns with the APGI core mission and provides a multimodal approach to targeting pancreatic cancer from either the epithelial or stromal compartment. Overall, APMA provides a world class resource from which to base novel targeted therapies in the era of personalised medicine and microenvironmental influence in this aggressive disease.
Vision and goals
We aim to better understand how the dynamic ECM landscape is linked to alterations in drug response and patient survival. By mapping the histological, immunohistochemical, and proteomic differences between normal fibrotic pancreatic tissue and matched pancreatic cancer we aim to define which ECM features are deregulated in this disease and reveal new ECM targets. Detailed comprehensive mapping of the topology and 3D structure of the ECM in native pancreatic tissue and pancreatic cancer, in correlation with clinicopathological and genetic sequencing data, has not been possible until now. The Garvan Institute of Medical Research, working with the Royal North Shore Hospital (RNSH) here in Australia are perfectly placed to achieve this, thereby establishing the first national and international comprehensive human pancreatic cancer ECM database.
We envisage that APMA will be an international resource held in Australia for pancreatic cancer matrix targeting, creating an international portal for matrix biology researchers and clinicians to interrogate and query disease progression, outcome, survival and relapse in the context of ECM composition and 3D matrix topology. Working with the clinical team at RNSH we will integrate our ECM findings with clinicopathological data including survival, relapse, and resistance, to identify ECM companion biomarkers and actionable targets that may be diagnostic and/or prognostic.
Prof. Paul Timpson, Dr. Thomas Cox, A/Prof. Marina Pajic, Prof. Anthony Gill, Dr. Brooke Pereira, Dr. David Herrmann, Prof. Jas Samra, Amber Johns, Gloria Jeong
Patient enrolment to date
To date, 35 highly fibrotic (15 PDAC) fresh human specimen sets (pancreatic tumour, adjacent non-neoplastic pancreas, and duodenum or spleen) have been collected from Whipple’s procedures at RNSH.
All collections have snap-frozen specimens from the fresh primary pancreatic tumour, as well as a matched adjacent non-neoplastic pancreas specimen and a duodenal or splenic specimen, which are available upon request via the APGI BioResource Request Form. The primary pancreatic tumour and adjacent non-neoplastic pancreas specimens were also formalin-fixed paraffin-embedded (FFPE) and embedded and frozen in OCT. For PDAC tumours, orthotopic and subcutaneous PDXs are set up. Successful PDXs are then serially passaged, with cryopreserved specimens available upon request. All specimens are also available upon request using the APGI BioResource Request Form.