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.
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.
Liu D, Sharbeen G, Phillips P, et al.
BMC Cancer. 2021 Nov 11;21(1):1199. doi: 10.1186/s12885-021-08952-9.
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.
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.
Dreyer SB, Pinese M, Jamieson NB, et al.
Ann Sug. 2020 Aug:272(2):366-376. doi: 10.1097/SLA.0000000000003143.
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.
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.
Kokkinos J, Ignacio RMC, Sharbeen G, Boyer C, et al.
Biomaterials. 2020 Jan 8;240:119742. doi: 10.1016/j.biomaterials.2019.119742.
Castillo L, Young AIJ, Mawson A, Schafranek P, et al.
Oncogene. 2020 Feb;39(8):1821-1829. doi: 10.1038/s41388-019-1091-0.
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
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.
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.
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
Jamieson NB, Upstill-Goddard R, Bailey PJ, et al.
Br J Surgery 2018 Jan; 105(2):e183-191. doi:10.1002/bjs.10772.
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’
Scarpa A, Chang DK, Nones K, et al
Nature. 2017 Oct 26;550(7677):548. doi:10.1038/nature24026.
Johns AL, Nicol D, Zeps N, Chalmers D.
Medicine and Law. Number 1 March 2017 Vol 36.
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
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
Scarpa A, Chang DK, Nones K, Corbo V, et al.
2017 Mar 02; 543(7643):65–71. doi:10.1038/nature21063
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
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
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