Category Archives: Pancreatic Cancer

News: Anti-fibrotic LOX family inhibitor program to progress to Phase Ib trial

Thomas R. Cox, Oct 2019

Following a successful Phase Ia trial of their oral anti-fibrotic systemic LOX inhibitor, Pharmaxis are now moving into a Phase Ib multiple ascending dose (MAD) study in healthy volunteers.

This is an exciting time for the Matrix and Metastasis team as we have been collaborating closely with Pharmaxis recently in developing a pre-clinical portfolio to help build a case for potentially transitioning this compound through to a clinical trial in pancreatic cancer patients. Pharmaxis is already seeking to progress this compound in the myelofibrosis space, and so working with our team, we are exploring the potential for this exciting anti-fibrotic compound in other cancer settings.

Pharmaxis Systemic LOX inhibitor

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Publication: CAF Subpopulations: A New Reservoir of Stromal Targets in Pancreatic Cancer

Thomas R. Cox, Oct 2019

CAF Subpopulations: A New Reservoir of Stromal Targets in Pancreatic Cancer

Working together with A/Prof Paul Timpson’s lab, we are pleased to announce that our recent review on targetting CAFs in pancreatic cancer has just been published in Trends In Cancer.

In this work we explore how different aspects of CAF heterogeneity are defined and how these manifest in multiple cancers, with a focus on pancreatic ductal adenocarcinoma (PDAC).

Mechanisms of CAF Heterogeneity

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

Thomas R. Cox, Aug 2019

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

We are super excited to announce that our recent work in close collaboration with A/Prof Paul Timpson has just been published in Nature Communications (view the full Open-Access article here)

In this work (which was a large international collaboration), co-led by our team and Paul Timpson’s team (also at the Garvan Institute), we show that remodeling of the stromal  tissue in and around pancreatic tumours may be the key to stopping their spread and improving chemotherapy outcomes.

Cancer cell CAF crosstalk

What we did

We already know that tumours are made up of heterogenous populations of cancer cells with different mutational landscapes. Furthermore, recently, the field has begun to realise that the cancer associated fibroblasts (CAFs) present in and around the tumour are also a diverse collection of  subpopulations.

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Publication: The Mini‐Organo: A rapid high‐throughput 3D coculture organotypic assay for oncology screening and drug development

Thomas R. Cox, Aug 2019

The Mini‐Organo: A rapid high‐throughput 3D coculture organotypic assay for oncology screening and drug development

Just published in Cancer Reports is our new protocol paper detailing the development of a rapid high-throughput (96wp) 3D organotypic coculture assay that is optimised for screening cancer cell and cancer-associated fibroblast response to drugs in physiologically relevant matrices.

Mini-Organo workflow

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Funding: Cancer Council NSW Project Grant

Thomas R. Cox, Mar 2019

Cancer Council NSW grants for innovative cancer research

CCNSW Logo

Great news! The Matrix & Metastasis Lab been awarded a three-year project grant from Cancer Council NSW to explore a new combination approach to treating pancreatic cancer.

The project will look at how to target the Lysyl Oxidase (LOX) family of enzymes in in pancreatic cancer with the goal of improving outcomes in patients.

Pancreatic cancer has one of the poorest survival rates of all cancer, with only 25% of people surviving one year after diagnosis and only 8% for five years. This project will look at the tissue in and around pancreatic cancers, which can affect how successful chemotherapy treatment is in a patient.

The aim is to combining biology and engineering to generate 3D models that mimic tumours, along with cutting edge imaging technology and mouse models, to investigate the potential of co-targeting the Lysyl Oxidase family together with already approved cancer drugs to improve patient outcome.

Thomas Cox CCNSW Awards Evening

Dr Thomas Cox receiving the award on behalf of the team at CCNSW’s annual Research Awards Evening.

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People: M&M 2019 Honours Students

Thomas R. Cox, Jan 2019

The Matrix and Metastasis group is excited to be welcoming two new Honours students to the team for 2019.

Yordanos Setargew (left) and Shivanjali Ratnaseelan (right) will both be joining us to spend the next 10 months in the lab as part of their UNSW Sydney, School of Medical Sciences (SoMS) Honours Program.

Yordanos Setargew Shivanjali Ratnaseelan

Yordanos will be looking at new ways to target the lysyl oxidase (LOX) family in pancreatic cancer, and Shivanjali will be looking at how the biomechanical properties of the tumour microenvironment alter breast cancer cell sensitivity to chemotherapy.

News: Anti-fibrotic LOX family inhibitor program to commence Phase I trials

Thomas R Cox, Nov 2018

We’re exited to reveal that we have been working hard with Pharmaxis on the development of their lysyl oxidase (LOX) systemic inhibitor for the potential use as a stromal co-targeting agent in pancreatic cancer.

Pharmaxis has developed an oral drug that inhibits all LOX family members, and which has shown to lead to significant reductions in fibrosis (scarring) in in-vivo models of kidney fibrosis, lung fibrosis, myelofibrosis and now with our help, in models of pancreatic cancer.

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Publication: Removing physiological motion from intravital and clinical functional imaging data

Thomas R. Cox, Jul 2018

Removing physiological motion from intravital and clinical functional imaging data

Galene is a new tool just published in eLife that can correct for physiological motion in live imaging data post-acquisition.

Galene Motion Correction Software

eLife digest

Understanding how molecules and cells behave in living animals can give researchers key insights into what goes wrong in diseases such as cancer, and how well potential treatments for these diseases work. Continue reading

People: Jessica joins M&M

Thomas R. Cox, Dec 2017

Jessica Chitty (Matrix and Metastasis Lab)I’m delighted to announce that Jessica Chitty will shortly be joining the lab as a postdoctoral research fellow. Jessica has just completed her Ph.D at the University of Queensland and is making the move south to join our team.

Having completed a degree in Biochemistry in the UK, and her Ph.D in Australia, Jessica brings experience in investigating the translational repurposing of key anti-cancer/antimycotic targets, along with significant expertise in enzyme biochemistry and molecular biology in the context of rational drug design, focusing towards translational research.

Jessica will focus her work on our ongoing interest into the lysyl oxidase family of enzymes and their role in pancreatic cancer.

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

Thomas R. Cox, Apr 2017

ROCK-ing pancreatic cancer to the core

Our new paper on short-term pulsed treatment, or ‘priming’ as a treatment strategy to boost chemotherapy has just been published in Science Translational Medicine.

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

The research, spearheaded by Dr. Paul Timpson and Dr. Marina Pajic here at the Garvan Institute of Medical Research in Sydney, has uncovered a promising new approach to treating pancreatic cancer. By targeting the tissue surrounding the tumour to make it ‘softer’, it leads to tumours being more responsive to chemotherapy.

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