The Role of the ECM in Lung Cancer Dormancy and Outgrowth
We are pleased to report that our recent in depth review on the role of the extracellular matrix (ECM) in Lung cancer, both in primary and metastatic settings has just been published as part of a special edition on ‘Revisiting Seed and Soil: A New Approach to Target Hibernating Dormant Tumor Cells‘ in Frontiers in Oncology: Molecular and Cellular Oncology.
Stromal cell diversity associated with immune evasion in human triple‐negative breast cancer
We are excited to have been part of a recent piece of work using single cell genomics to map the different cell types present with triple negative breast cancer which has recently been published in EMBO.
The work, led by Alex Swarbrick and his team here at the Garvan uncovered four new subtypes of cells within triple negative breast cancer, which contain promising new therapeutic targets for the aggressive disease. These cells produces molecules that suppress immune cells, which may help cancer cells evade the body’s immune system, and the work could lead to a new class of therapies for triple negative breast cancer.
Plasma polymerized nanoparticles effectively deliver dual siRNA and drug therapy in vivo
We are delighted to have been part of an exciting study looking into the potential of a new class of multifunctional nanocarrier to deliver dual siRNA and drug therapy to breast tumours which was recently published in Scientific Reports.
The work was led by our collaborators Miguel Santos and Steven Wise from the Applied Materials Group at the University of Sydney who pioneered the development of these novel multifunctional nanocarriers.
Cancer Metastasis: The Role of the Extracellular Matrix and the Heparan Sulfate Proteoglycan Perlecan
Our recent review paper in collaboration with colleagues in Sydney and Melbourne on the role of the ECM and in particular the Heparan Sulphate Proteoglycan, Perlecan, in cancer and cancer metastasis, has just been published in Frontiers in Oncology.
Targeting the lysyl oxidases in tumour desmoplasia
Our recent review discussing the importance, and also the therapeutic potential of inhibiting the lysyl oxidase (LOX) family of enzymes as a stromal targeting therapy has just been published in Biochemical Society Transactions.
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.
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.
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.
LOXL1 Is Regulated by Integrin α11 and Promotes Non-Small Cell Lung Cancer Tumorigenicity
Our lab has contributed to a recent paper by Zeltz and colleagues looking at the interplay between Lysyl Oxidase Like 1 (LOXL1) and Integrin α11 in Non-Small Cell Lung Cancer (NSCLC). The work was published in the Open-Access journal Cancers.
Proteomic Profiling of Human Prostate Cancer-associated Fibroblasts (CAF) Reveals LOXL2-dependent Regulation of the Tumor Microenvironment
A new paper has just been published revealing the role of Lysyl Oxidase Like 2 (LOXL2) in the remodelling of the prostate cancer microenvironment. The work, carried out in collaboration with lead researchers from the Cancer Program, Biomedicine Discovery Institute at Monash University has just been published in Molecular and Cellular Proteomics.
Targeting promiscuous heterodimerization overcomes innate resistance to ERBB2 dimerization inhibitors in breast cancer
We have just published a new paper in Breast Cancer Research in collaboration with lead researcher Dr. David Croucher from the Garvan Institute, looking at how and why ERBB2 (HER2) positive breast cancer cells develop resistance to targeted therapies such as trastuzumab (Herceptin™).
Computational model of the interplay between the ECM and drug activated MAPK‐JNK signalling network.
At their simplest, cells follow a set of rules governed by their genetic code. These rules, which are executed by the protein‐based signalling networks that the genes encode, control the assimilation of information and decision‐making processes that shape a cell’s response to their surroundings.
Cancer cell ability to mechanically adjust to extracellular matrix stiffness correlates with their invasive potential
Just published in Molecular Biology of the Cell is our recent paper looking at the effect of extracellular matrix stiffness on the intrinsic biomechanical properties of cancer cells. Led by Professors Janine Erler (Biotech Research & Innovation Centre) and Lene Oddershede (Niels Bohr Institute) both from the University of Copenhagen, the study combines optical tweezers–based microrheology and deformability cytometry with 3D biological models to dissect how cancer cells biomechanically interact with and respond to the stiffness of the microenvironment they are within.
Optical Tweezers Schematic for measuring intracellular viscosity
The results show that invasive cancer cells adjust their intracellular and overall viscoelasticity to ECM density, and that cancer cell viscosity increases during invasion into 3D collagen matrices.