PERSONALISED CANCER THERAPEUTICS
Pancreatic cancer is one of the deadliest forms of cancer, which still kills 94% 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.
Our vision is to build on our recent discoveries in the field of cancer genomics (published in Nature 2012, 2013, 2015 and 2016) to develop 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.
Cutting edge tools to study pancreatic cancer:
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, and are readily available to the wider research community; please see: http://www.pancreaticcancer.net.au/bioresource-pdcls/
The main goals of our group are to:
1- Prioritise and validate novel targets and therapeutic regimens in early development for the treatment of pancreatic cancer. The proposed research is a natural continuation of our collaborative successes in pancreatic cancer genomics (eg. Nature 2015) aimed at improving treatment options for pancreatic cancer.
2- Expand the portfolio and clinical relevance of preclinical models of pancreatic cancer to serve as a platform for evaluating and prioritising novel therapeutic strategies. Our team is optimising the use of new fluorescent pancreatic PDX models with intravital biosensor imaging (with collaborator Dr Timpson) to take cancer biology from static 2D assessment to dynamic 3D live imaging of pathway activity, as highlighted by joint publication in Science Translational Medicine 2017.
3- Understand the molecular evolution of tumours following treatment and mechanisms that underline de novo and acquired resistance, in order to further refine treatment options for 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.
Chou A, Froio D, Nagrial AM, Parkin A, Murphy KJ, Chin VT, Wohl D, Steinmann A, Stark R, Drury A, Walters SN, Vennin C, Burgess A, Pinese M, Chantrill LA, Cowley MJ, Molloy TJ; Australian Pancreatic Cancer Genome Initiative (APGI), Waddell N, Johns A, Grimmond SM, Chang DK, Biankin AV, Sansom OJ, Morton JP, Grey ST, Cox TR, Turchini J, Samra J, Clarke SJ, Timpson P, Gill AJ, Pajic M. Tailored first-line and second-line CDK4-targeting treatment combinations in mouse models of pancreatic cancer. Gut 2017 Oct 28. [Epub ahead of print]
Vennin C, Chin VT, Warren S, Lucas MC, Herrmann D, Melenec P, Walters SN, Magenau A, Allam AH, McCloy RA, Conway JRW, Pinese M, Boulghourjian A, Zaratzian A, Heu C, Nagrial AM, Chou A, Steinmann A, Drury A, Froio D, Giry-Laterriere M, Harris NLE, Mcghee EJ, Whan R, Grey S, Johns AL, Samra JS, Chantrill L, Gill AJ, Biankin AV, APGI, Wang Y, Evans TRJ, Anderson KI, Samuel MS, Burgess A, Sansom OJ, Morton JP, Pajic M*, Timpson P*. * Co-last and co-corresponding authors. Transient tissue ‘priming’ via ROCK inhibition uncouples pancreatic cancer progression, sensitivity to chemotherapy and the onset of the metastatic niche. Science Translational Medicine 2017 9(384). pii: eaai8504.
Pajic M, Froio D, Daly S, Doculara L, Millar EK, Graham P, Drury A, Steinmann A, de Bock CE, Boulghourjian A, Zaratzian A, Carroll SL, Toohey JM, O’Toole SA, Harris AL, Buffa FM, Gee HE, Hollway G, Molloy TJ. miR-139-5p modulates radiotherapy resistance in breast cancer via repression of multiple DNA repair and reactive oxygen species defence gene networks. Cancer Research (Accepted)
Pajic M, Blatter S, Guyader C, Gonggrijp M, Kersbergen A, Sol1 W, Drost R, Jonkers J, Borst P, Rottenberg S. Selected alkylating agents can overcome drug tolerance of G0-1 like tumor cells and eradicate BRCA1-deficient mammary tumors in mice. Clinical Cancer Research 2017 Aug 18. [Epub ahead of print]
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.
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, 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
More Garvan Publications
Staff in the Group