Australia Pancreatic Cancer Genome Initiative

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Published: 18 Jul 2012
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Dr Marina Pajic – The Garvan Institute of Medical Research, Darlinghurst, Australia

As part of the International Cancer Genome Consortium, the Australia Pancreatic Cancer Genome Initiative (APGI) is working to develop personalised medicines for pancreatic cancer patients.

Dr Marine Pajic discusses her work carrying out preclinical studies to validate new agents proposed for personalised pancreatic cancer treatments.

Thanks to the positive results of these studies using patient DNA and RNA to identify treatment targets, the APGI is expecting to launch the IMPACT trial of personalised medicines at the end of the year.

EACR 2012

Australia Pancreatic Cancer Genome Initiative

Dr Marina Pajic – The Garvan Institute of Medical  Research, Darlinghurst, Australia

Hello, Dr Pajic. We’re at the EACR in Barcelona and you gave a very nice presentation on new therapeutic strategies for pancreatic cancer because for pancreatic cancer we don’t have very much. Could you discuss a bit about your presentation?

Our group, which is led by Professor Andrew Biankin, we work together with Professor Sean Grimmond at the University of Queensland, so together we form what is called the Australian Pancreatic Cancer Genome Initiative. As a member of the large International Cancer Genome Consortium, our aim is really to fully characterise a whole range of aberrations in a large number of pancreatic cancer samples. What we would like to do with all this data is to really use it to try and identify some new strategies for pancreatic cancer treatment. This is really because the current model, the way it works, is the one drug fits all system; it just doesn’t seem to work for pancreatic cancer. So we’d like to develop a more personalised approach where you really try to identify the right drug for the right patient and hopefully improve the patient outcomes.

So for pancreatic cancer there are not very many options available so have you started to identify some maybe targetable, druggable targets?

Yes, that’s really where I come in, I guess, because I’m mostly working with pre-clinical models for pancreatic cancer so obviously all of these new treatment strategies need to be tested in an earlier model before they are given to patients. So we’re using both mouse models of pancreatic cancer as well as some primary cancer cell lines that I have generated from patient samples. So here we have a really nice resource where we have both the patient tumour DNA, patient germline DNA, so this is the healthy DNA from the patient, we have the primary xenograft model, which is the mouse model for pancreatic cancer, as well as cell lines. So you can really directly identify a mutation of interest and then test it in the pre-clinical setting.

So you’re doing genome sequencing, copy number variation.

Correct, also RNA analysis, methylome analyses and then we’re trying to really integrate all that data together to identify some molecular phenotypes.

And have you found any specific phenotypes to pancreatic cancer?

Yes, we are identifying, so we have identified maybe four or five subgroups that potentially could benefit from more targeted therapies but, again, this is quite early so I’m working on that now in the pre-clinical testing side of things. Hopefully the good news about all of this is that some of these drugs are actually used for clinical management of patients with other cancer types. So it shouldn’t be too difficult to use them for pancreatic cancer patients.

So are you finding that pancreatic cancer could now be maybe divided into subgroups with different… maybe some being more aggressive, or…?

I think it’s going to be unlike, maybe, breast where there are large portions of patients that fit into a specific subgroup. With pancreatic cancer it’s going to be more of a plethora of a range of rarer phenotypes, so things that are maybe 5-10% per phenotype. So it will be really tricky to identify some of them, I guess.

How long do you think it is before maybe you’re going to take something into a clinical trial?

We have personalised medicine clinical trials starting towards the end of the year in Australia so we are looking at implementing these so this is called the IMPACT trial. So it is actually going to be directly transferable to the clinic.

Great, thank you. We’ll see what happens.