A first-in-class pan-lysyl oxidase inhibitor impairs stromal remodeling and enhances gemcitabine response and survival in pancreatic cancer

The Impact of Molecular Subtyping on Pathological Staging of Pancreatic Cancer

Dyer SB, Rae S, Bisset K, et al. 
Ann Surg. 2023 Feb 1; 227 (2):e396-e405. doi:10.1097/SLA0000000000005050. 

Gene Expression Profiling Mucinous Ovarian Tumors and Comparison with Upper and Lower Gastrointestinal Tumors Identifies Markers Associated with adverse Outcomes

Prognostic implications of microRNA-21 overexpression in pancreatic ductal adenocarcinoma: an international multicentre study of 686 patients

Ali A, Jamieson NB, Khan IN, et al. 
Am J Cancer Res. 2022 Dec 15;12(12):5668-5683.

The Right Treatment Strategy for the Right Patient: A Biomarker-Drive Approach to Neoadjuvant vs. Surgery First Management of Resectable and Borderline Resectable  Pancreatic Cancer

Nahm C, Turchini J, Sahni S, …Chou A, Samara JS, Gill AJ, et al. 
Cancer (Basal). 2022 Jul 25;14(15):3620. doi: 10.3390/cancers14153620.

Neoantigen quality predicts immunoediting in survivors of pancreatic cancer

Łuksza M, Sethna ZM, Rojas LA,..Gill A, et al. 
Nature. 2022 Jun;606(7913):389-395. doi: 10.1038/s41586-022-04735-9.
The authors investigated whether immunoediting occurs in human cancers. Using PDAC samples from Short-Term and Long-Term survivors, the authors found that when the immune system recognises an immunogenic antigen (neoantigen) in a primary tumour, this induces the antigen to be subsequently eliminated in the recurrent tumour. Tumours evolve under a stronger immune pressure lose more immunogenic neoantigens, thus show less heterogeneity. The authors further propose that a fundamental function of the immune system is to maintain integrity of the host genome.

ROR1 and ROR2 expression in pancreatic cancer

Liu D, Sharbeen G, Phillips P, et al.
BMC Cancer. 2021 Nov 11;21(1):1199. doi: 10.1186/s12885-021-08952-9. 

Genomic and Molecular Analyses Identify Molecular Subtypes of Pancreatic Cancer Recurrence

Dreyer SB, Upstill – Goddard R, Legrini, et al.
Gastroenteroloy. 2021 Sep 14;S0016-5085(21)03522-8. doi: 10.1053/j.gastro.2021.09.022.

Intravital imaging technology guides FAK-mediated priming in pancreatic cancer precision medicine according to Merlin status

Murphy KJ, Reed DA, Vennin C, et al.
Sci Adv. 2021 Oct;7(40):eabh0363. doi: 10.1126/sciadv.abh0363.
The authors highlight the potential clinical benefits of utilising targeted short-term inhibition of focal adhesion kinase (FAK) in pancreatic ductal adenocarcinoma (PDAC), to pre-treat the environment around the tumour to increase chemosensitivity of the cancer. Transient FAK inhibition ‘priming’ resulted in reduction of PDAC metastatic spread and sensitised the cells to subsequent chemotherapy treatment. FAK inhibition priming was also found to render a subtype of pancreatic cancer patients with high FAK and low expression of the tumour suppressor Merlin, more responsive to chemotherapy.
Garvan News: Pancreatic Cancer ‘priming’ may make chemotherapy more effective

Significant detection of new germline pathogenic variants in Australian Pancreatic Cancer Screening Program Participants

Murali K, Duarte TM, Nikfarjam M, et al.
Hered Cancer Clin Pract. 2021 Aug 16;19(1):33. doi: 10.1186/s13053-021-00190-1.

Cancer-Associated Fibroblasts in Pancreatic Ductal Adenocarcinoma Determine Response to SLC7A11 Inhibition

Sharbeen G, McCarroll JA, Akerman A, et al.
Cancer Res. 2021 Jul 1;18(13):3461-3479. doi: 10.1158/0008-5472.CAN-20-2496.

DNA methylation patterns identify subgroups of pancreatic neuroendocrine tumors with clinical association

Lakis V, Lawlor RT, Newell F, Patch AM, et al.
Commun Biol. 2021 Feb 3;4(1):155. doi: 10.1038/s42003-020-01469-0.

Targeting DNA Damage Response and Replication Stress in Pancreatic Cancer

Dreyer SB, Upstill-Goddard R, Paulus-Hock V, et al.
Gastroenterology. 2020 Oct 8:S0016-5085(20)35229-X. doi: 10.1053/j.gastro.2020.09.043.

Precision Oncology in Surgery: Patient Selection for Operable Pancreatic Cancer

Dreyer SB, Pinese M, Jamieson NB, et al.
Ann Sug. 2020 Aug:272(2):366-376. doi: 10.1097/SLA.0000000000003143.

HNF4A and GATA6 Loss Reveals Therapeutically Actionable Subtypes in Pancreatic Cancer

Brunton H, Caligiuri G, Cunningham R, Upstill-Goddard R, et al.
Cell Rep 2020 May 12;31(6):107625. doi: 10.1016/j.celrep.2020.107625.

Pan-cancer analysis of whole genomes

ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium.
Nature. 2020 Feb;578(7793):82-93. doi: 10.1038/s41586-020-1969-6.
The APGI contributed 175 genomes to the Pan-Cancer Project, a global effort that has created a resource of over 2600 cancer genome of 38 different tumour types. Researchers across the globe will use the database to study pancreatic and other cancers, bringing better diagnosis and treatments within reach.
Garvan News: Garvan contributes to global cancer genome ‘map’

Pancreatic resection in patients with synchronous extra-pancreatic malignancy: outcomes and complications

Mehta S, Tan GI, Nahm CB, et al.
ANZ J Sure. 2020 Jan 13. doi: 10.1111/ans.15651.

Targeting the undruggable in pancreatic cancer using nano-based gene silencing drugs

Kokkinos J, Ignacio RMC, Sharbeen G, Boyer C, et al.
Biomaterials. 2020 Jan 8;240:119742. doi: 10.1016/j.biomaterials.2019.119742.

MCL-1 antagonism enhances the anti-invasive effects of dasatinib in pancreatic adenocarcinoma

Castillo L, Young AIJ, Mawson A, Schafranek P, et al.
Oncogene. 2020 Feb;39(8):1821-1829. doi: 10.1038/s41388-019-1091-0.

Development and validation of a targeted gene sequencing panel for application to disparate cancers

McCabe MJ, Gauthier MA, Chan CL, Thompson TJ, et al.
Sci Rep. 2019 Nov 19;9(1):17052. doi: 10.1038/s41598-019-52000-3.

Genetic counselling and personalised risk assessment in the Australian pancreatic cancer screening program

Dwarte T, McKay S, Johns A, Tucker K, et al.
Hered Cancer Clin Pract. 2019 Oct 23;17:30. doi: 10.1186/s13053-019-0129-1.
Screening trial participants report their experience of genetic counselling (and testing where appropriate) for pancreas cancer (PC) susceptibility. They report multiple benefits, including improved understanding of genetic and environmental risks, reassurance and a motivation to help younger generations. Most are interested in genetic testing for PC susceptibility and want genetics review when further testing becomes available. We also assess the utility of PancPRO, a PC risk estimation model, to estimate a person’s individual risk based on their family history. Personalised risk assessments may improve risk communication and patient education during genetic counselling consultations.

CAF hierarchy driven by pancreatic cancer cell p53-status creates a pro-metastatic and chemoresistant environment via perlecan

Vennin C, Mélénec P, Rouet R, Nobis M, et al.
Nat Commun. 2019 Aug 12;10(1):3637. doi: 10.1038/s41467-019-10968-6.
Aggressive pancreatic cancer cells change their environment (matrix) to enable easier spreading of the cancer (metastasis). This is done by a production of a molecule called ‘perlecan’ to remodel the matrix, easily allowing metastasis and also protecting them against chemotherapy. Together with targeting the cancer cells themselves with chemotherapy, there are important benefits in targeting the cells that produce the matrix, namely fibroblasts.
Garvan News: Key to targeting the spread of pancreatic cancer

Three hypomethylated genes were associated with poor overall survival in pancreatic cancer patients

Chen H, Kong Y, Yao Q, et al.
Aging (Albany NY). 2019 Feb 1;11(3):885-897. doi: 10.18632/aging.101785.

Tailored first-line and second-line CD4-K-targeting treatment combinations in mouse models of pancreatic cancer

Chou A, Froio D, Nagrial AM, et al.
Gut. 2018 Dec;67(12):2142-2155. doi 10.1136/gutjnl-2017-315144.

ROBO2 is a stroma suppressor gene in the pancreas and acts via TGF-β signalling

Pinho AV, Van Bulck M, Chantrill L, Arshi M, et al.
Nat Commun. 2018 Nov 30;9(1):5083. doi: 10.1038/s41467-018-07497-z.

Provenance and risk in transfer of biological materials

Nielsen J, Bubela T, Chalmers DRC, Johns A, et al.
PLoS Biol. 2018 Aug 13;16 (8):e2006031. doi: 10.1371/journal.pbio.2006031
The paperwork required for contemporary research has drastically increased. One example is a Material transfer agreement (MTA) which is a common vehicle for exchanging materials. This paper investigates ways to minimise delays in research that requires access to materials on reasonable terms.
APGI News: Cutting through the red tape in sharing material for research

Defining the molecular pathology of pancreatic body and tail adenocarcinoma

Jamieson NB, Upstill-Goddard R, Bailey PJ, et al.
Br J Surgery 2018 Jan; 105(2):e183-191. doi:10.1002/bjs.10772.

Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer

Balachandran VP, Luksza M, Zhao JN, et al.
Nature. 2017 Nov 23; 551-516. doi:10.1038/nature24462.
Garvan News: Long-term survivors of pancreatic cancer have ‘built-in immunotherapy’

Corrigendum: Whole-genome landscape of pancreatic neuroendocrine tumours

Scarpa A, Chang DK, Nones K, et al
Nature. 2017 Oct 26;550(7677):548. doi:10.1038/nature24026.

The Path to reducing duplication of Human Research Ethics review in Australia

Johns AL, Nicol D, Zeps N, Chalmers D.
Medicine and Law. Number 1 March 2017 Vol 36.

Lost in translation: returning germline genetic results in genome-scale cancer research

Johns AL, McKay SH, Humphris JL, Pinese M, et al.
Genome Med. 2017 Apr 28; 8(41). doi: 1186/s13073-017-0430-4.
The complexities involved in returning genome-scale research results to study participants and the assessment of the impact on their clinical care and health outcomes have been analysed. The benefit of returning results can be substantial and valuable, even though it is labour-intensive and the rates of finding clinically applicable information are likely to be low in large-scale genomic studies.
Garvan News: The importance of returning research results to study participants

SerpinB2 regulates stromal remodelling and local invasion in pancreatic cancer

Harris NL, Vennin C, Conway JR, Vine KL, et al.
Oncogene. 2017 Mar 27. doi: 10.1038/onc.2017.63.

Transient tissue priming via ROCK inhibition uncouples pancreatic cancer progression, sensitivity to chemotherapy, and metastasis.

Vennin C, Chin VT, Warren SC, Lucas MC, et al.
Sci Transl Med. 2017 Apr 5;9(384). pii: eaai8504. doi: 10.1126/scitranslmed.aai8504
This paper uncovers a promising new approach to treating pancreatic cancer by targeting the tissue around the tumour. This is done by a course of fasudil which is a drug that makes tumours softer and makes the blood vessels around tumours ‘leaky’. Subsequent treatment with standard-of-care chemotherapy for pancreatic cancer resulted in double the survival time and impaired metastasis.
Garvan News: A one-two punch for pancreatic cancer: ‘softening’ tumours before chemo markedly improves survival

Whole-genome landscape of pancreatic neuroendocrine tumours

Scarpa A, Chang DK, Nones K, Corbo V, et al.
2017 Mar 02; 543(7643):65–71. doi:10.1038/nature21063

Hypermutation in Pancreatic Cancer

Humphris, JL, Patch A, Nones K, Bailey PJ, et al.
Gastroenterology. 15 Nov 2016. doi.org/10.1053/j.gastro.2016.09.060

Ampullary cancers harbor ELF3 tumor suppressor gene mutations and exhibit frequent WNT dysregulation

Gingras M, Covington KR, Chang DK, Donehower LA, et al.
Cell Rep Feb 2016;14(4):907-19 doi:10.1016/j.celrep.2015.12.005

Genomic analyses identify molecular subtypes of pancreatic cancer

Bailey P, Chang DK, Nones K, Johns A.L. et al.
Nature Feb 2016 doi:10.1038/nature16965
This paper outlines the most in-depth analysis of pancreatic cancer, re-classifying this disease into four subtypes, each with its own genetic make-up and distinct behaviour. This gives us insight into why tumours seem to act differently in individual patients.
APGI News: Ground breaking research – but what does this mean for pancreatic cancer patients?

Precision medicine for advanced pancreas cancer: The Individualized Molecular Pancreatic Cancer Therapy (IMPaCT) Trial

Chantrill LA, Nagrial AM, Watson C, Johns AL, et al.
Clin Cancer Res. 2015 Apr 20
ABC News article: Health report on Learning from failure

Whole genomes redefine the mutational landscape of pancreatic cancer

Waddell N, Pajic M, Patch A, Chang D, et al.
Nature. 26 Feb 2015; 518(7540):459-501. doi:10.1038/nature14169 
The most in-depth analysis yet of 100 pancreatic cancer genomes has been done and it highlights 4 subtypes that my help guide future patient treatment.
Garvan News: How the landscape of the pancreatic cancer genome is coming into view