Category Archives: Breast Cancer

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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Publication: Targeting promiscuous heterodimerization overcomes innate resistance to ERBB2 dimerization inhibitors in breast cancer

Thomas R. Cox, Mar 2019

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™).

Promiscuity of the ERBB2 receptor in breast cancer

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Publication: Cancer cell ability to mechanically adjust to extracellular matrix stiffness correlates with their invasive potential

Thomas R. Cox, Oct 2018

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

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.

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Publication: Tumor endothelial marker 8 promotes cancer progression and metastasis

Thomas R. Cox, Jul 2018

Tumor endothelial marker 8 promotes cancer progression and metastasis

Our new paper has just been published in Oncotarget. In this study, we show that Tumor endothelial marker 8 (TEM8) regulates the expression of multiple genes. In particular, we observed that the most common expression changes conserved between breast and colorectal cancer are involved in regulation of the cell cycle. In line with the microarray results we show that TEM8 regulates cancer cell proliferation and primary tumor growth. Since TEM8 KO tumors presented with fewer blood vessels we hypothesize that TEM8 contributes to the regulation of angiogenesis, likely by being secreted by cancer cells to alter endothelial cell migration and thereby supporting growth of the tumor. Moreover, we confirm that TEM8 is an important player in driving tumor cell invasion and metastatic dissemination in breast cancer.

Tumor endothelial marker 8 promotes cancer progression and metastasis

Proposed mechanism behind the impact of TEM8 on breast and CRC cancer progression.

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Funding: Susan G. Komen® Career Catalyst Research Grant

Susan G Komen logoThomas R. Cox, Sep 2017

We’re delighted to announce the we have been awarded a research grant from the Susan G. Komen Foundation, the world’s leading breast cancer organisation.

The grant will support a project investigating how stiffness in breast tissue can drive the aggressive behaviour of cancer cells, and how tissue stiffness impacts on the effectiveness of breast cancer treatments

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Matrix: Dissolved – ABC Radio Network Health Report

ABC Radio National LogoThomas R. Cox, July 2017

I was recently invited to chat with Norman Swan on ABC Radio National’s Health report about some of the recent work we have been doing on the Extracellular Matrix in cancer.

The extracellular matrix or the matrix is the web- or mesh-like structure that encases the cells in the tissues and organs of our body.

ISDoT - Decellularised Extracellular Matrix

Image: Mayorca-Guiliani AE, Madsen CD, Cox TR et al. Nature Medicine (2017)

We recently developed a new technique which dissolves the cells from tumours to leave behind this matrix, allowing us to study it in unprecedented detail – and we discuss the potential of these research outcomes. Continue reading

Publication: ISDoT – in situ decellularization of tissues for high-resolution imaging and proteomic analysis of native extracellular matrix

Thomas R. Cox, Jun 2017

“We’re seeing things we’ve never seen before”: groundbreaking new technique sheds light on the ‘matrix’ surrounding our cells

Our most recent research  has just been published in Nature Medicine.

In our  paper we describe a new and intuitive new way to dissolve cells from tissues, leaving behind the extracellular matrix (ECM) or ‘matrix’.

The matrix is made up of 100’s of differing building blocks and surrounds the cells in our body. It is incredibly important in the progression and spread of cancer – but up until now it has been notoriously difficult to study in detail.

ISDoT - Decellularised Extracellular Matrix

Image: Mayorca-Guiliani AE, Madsen CD, Cox TR et al. Nature Medicine (2017)

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Funding: NHMRC New Investigator Grant to Thomas Cox

NHMRC Logo 1Thomas R. Cox, Dec 2017

We’re delighted to announce the we have been awarded a New Investigator Project Grant from the National Health and Medical Research Council (NHMRC).

The grant will support a project investigating how  targeting tumour tissue stiffness can increase the efficacy of currently approved therapies in solid cancers. Continue reading