BSB Seminar: Deconstructing Solid Tumour Heterogeneity: The Matrix Perspective

Synopsis

Homeostasis of the extracellular matrix is critical for correct organ and tissue function. Both the biochemical and biomechanical properties of the matrix contribute to modulating the behaviour of resident cells and are more than just passive bystanders. In tissue diseases such as cancer, we have shown that the matrix undergoes significant change. These changes, driven by both tumour and local and recruited stromal cells, feed into the pathological progression of the disease.

Work from our lab has shown that the matrix and matrix remodelling can both promote and restrict tumour progression. Through deploying multiple approaches to characterise tumour matrix remodelling, including the development of new technologies to visualise and catalogue the matrix over both time and space, and subsequently recapitulate these microenvironments in vitro, we are gaining insight into the factors that shape the development, evolution and cellular heterogeneity of a tumour, as well as its response to a particular therapy.

The non-selective depletion of the matrix has yielded paradoxical results, often accelerating progression. Instead, we have shown that more nuanced approaches to normalising biochemistry and biomechanics, rather than depleting the matrix results in favourable outcomes. As such, co-targeting the changing matrix in cancer, as well as the cellular response to the remodelled tumour matrix offer powerful approaches to improve therapy outcome for patients.

Biography

A/Prof. Thomas Cox is a cancer cell biologist working in the field of the extracellular matrix and matrix remodelling in the progression and metastasis of solid tumours. He graduated with a Ph.D. from the University of Durham, UK in 2008, followed by PostDoc positions at the Institute of Cancer Research in London, UK and Copenhagen University, Denmark. In 2016 he was recruited to the Garvan to establish his own independent research group. 

Thomas leads the Matrix and Metastasis Lab, Part of the Dynamic Cancer Ecosystems Program at the Garvan Institute and The Kinghorn Cancer Centre. His labs creative research program integrates matrix biology with precision oncology to make fundamental advances in personalised stromal targeting in breast, pancreatic and lung tumours.