Pancreatic cancer is one of the deadliest forms of cancer, which still kills 95% of the people it afflicts. The average survival of metastatic pancreatic cancer patients, even with treatment is only 6 months and novel treatment approaches are desperately needed.
The vision of our group is to build on our recent discoveries in the field of cancer genomics (published in Nature 2012, 2013, 2015 and 2016) to develop and test novel personalised approaches for the treatment of both primary operable and metastatic pancreatic cancer. Our team is multidisciplinary, comprising individuals from diverse disciplines ranging from basic biology, laboratory discovery and preclinical testing, biomarker development and implementation.
We have established a unique Australian resource, comprising of well annotated patient-derived xenografts of pancreatic cancer and a large well annotated panel of patient-derived cell lines from the patients that have been sequenced as part of the International Cancer Genome Consortium. Collectively, these models represent an invaluable resource of renewable material for the discovery of biomarkers and testing novel therapeutic combinations, a key goal of our group. Second major research interest involves elucidating the mechanisms of treatment-induced alterations in cell signalling and the subsequent development of therapeutic resistance in pancreatic cancer. The significance of our work is that the right treatments are given to the right patients where therapy is tailored according to the biology of each individual patient tumour.
Bailey P, Chang DK, Nones K, Johns AL, Patch AM, Gingras MC, Miller DK, Christ AN, Bruxner TJ, Quinn MC, Nourse C, Murtaugh LC, Harliwong I, Idrisoglu S, Manning S, Nourbakhsh E, Wani S, Fink L, Holmes O, Chin V, Anderson MJ, Kazakoff S, Leonard C, Newell F, Waddell N, Wood S, Xu Q, Wilson PJ, Cloonan N, Kassahn KS, Taylor D, Quek K, Robertson A, Pantano L, Mincarelli L, Sanchez LN, Evers L, Wu J, Pinese M, Cowley MJ, Jones MD, Colvin EK, Nagrial AM, Humphrey ES, Chantrill LA, Mawson A, Humphris J, Chou A, Pajic M et al. Genomic analyses identify molecular subtypes of pancreatic cancer. Nature 2016 531(7592):47-52
Waddell N, Pajic M, Patch AM, Chang DK, Kassahn KS, Bailey P, Johns AL, Miller D et al. Whole genomes redefine the mutational landscape of pancreatic cancer. Nature 2015 518(7540):495. * Significant national coverage, including interviews with Dr Pajic for SBS and Channel 7 national news.
Al-Ejeh F, Pajic M, Shi W, Kalimutho M, Miranda M, Nagrial AM, Chou A et al. Gemcitabine and CHK1 inhibition potentiate EGFR-directed radioimmunotherapy against pancreatic ductal adenocarcinoma. Clinical Cancer Research 2014 20(12):3187.
Alexandrov LB, Nik-Zainal S, Wedge DC, Aparicio S, Behjati S, Biankin AV, Bignell GR, Bolli N, Borg A, Børresen-Dale A-L, Boyault S, Burkhardt B, Butler AP, Caldas C, Davies HR, Desmedt C, Eils R, Eyfjörð JE, Foekens JA, Greaves M, Hosoda F, Hutter B, Ilicic T, Imbeaud S, Imielinsk M, Jäger N, Pajic M. et al. Signatures of mutational processes in human cancer. Nature 2013; 500(7463):415-21.
Chang DK, Johns AL, Scarlett CJ, Pajic M. et al. Molecular Pathological Phenotypes and Outcome in Adenocarcinoma of the Ampulla of Vater. Journal of Clinical Oncology 2013; 31(10):1348-56.
Biankin AV, Waddell N, Kassahn KS, Gingras MC, Muthuswamy LB, Johns AL, Miller DK, Wilson PJ, Patch AM, Wu J, Chang DK, Cowley MJ, Gardiner BB, Song S, Harliwong I, Idrisoglu S, Nourse C, Nourbakhsh E, Manning S, Wani S, Gongora M, Pajic M. et al. Genomic Analysis Reveals Roles for Chromatin Modification and Axon Guidance in Pancreatic Cancer. Nature 2012 491(7424):399-405.
Pajic M, Scarlett CJ, Chang DK et al. Preclinical strategies to define predictive biomarkers for therapeutically relevant cancer subtypes. Human Genetics 2011; 130(1):93
Pajic M, Murray J, Marshall GM, Cole SP, Norris MD, Haber M. ABCC1 G2012T single nucleotide polymorphism is associated with patient outcome in primary neuroblastoma and altered stability of the ABCC1 gene transcript. Pharmacogenetics and Genomics 2011; 21(5):270
Pajic M, Kersbergen A, van Diepen F et al. Tumor-initiating cells are not enriched in cisplatin-surviving BRCA1;p53-deficient mammary tumor cells in vivo. Cell Cycle 2010; 9(18):3780
Pajic M, Iyer JK, Kersbergen A, et al. A moderate increase in Mdr1a/1b expression causes in vivo resistance to doxorubicin in a mouse model for hereditary breast cancer Cancer Research (2009) 69 16:6396
Rottenberg S, Nygren AOH, Pajic M et al. Selective induction of chemotherapy resistance of mammary tumors in a conditional mouse model for hereditary breast cancer. Proc Natl Acad Sci USA 2007;104(29):12117
More Garvan Publications
Staff in the Group
In the News
NHMRC funding success for Garvan researchers - Nov 09, 2015
Mark Cowley and Marina Pajic top-ranked applicants for Cancer Institute NSW Fellowships - Apr 08, 2014
Angela Chou and Lee Marshall win 2013 Castle Harlan Award - Nov 15, 2013
Potential treatment for a specific kind of pancreatic cancer - Sep 16, 2013
International team reveals 21 ‘signatures’ in 30 common cancers - Aug 15, 2013