Seminar

Targeting cancer-associated fibroblasts to deter tumour progression

Fernando Calvo, PhD

The Tumour Microenvironment Team uses a wide range of techniques from conventional cell and molecular biology, through in vivo models and analysis of clinical material to study the multicellular context of solid tumours and understand the molecular mechanisms regulating cancer progression, dissemination and response to therapy. To achieve this, we investigate the environmental cues (chemical or physical) and signals from malignant cells that lead to the emergence of tumour-promoting phenotypes in otherwise healthy cells of the tumour microenvironment, with a particular focus in cancer-associated fibroblasts (CAF).The ultimate goal of these studies is to yield important insights into cancer biology leading to improved strategies for cancer therapy. Here, he will present his advances in the molecular and functional characterisation of CAFs, describing how CAFs contribute to tumour progression and the crucial molecular mechanisms that modulate their behaviour. In particular, we will delineate the importance of mechanotransduction and cytoskeletal rearrangements in CAF biology (Calvo Nat Cell Biol 2013; Calvo Cell Reports 2015) and describe recent findings on the unpredicted link between HSF1, Wnt signalling and YAP/TAZ relevant for the generation of tumour-promoting CAFs (Ferrari Nat Comm 2019). Finally, we will present ongoing work on the role of stromal HSF1 in modulating aggressive tumour microenvironments and the potential of epigenetic reprogramming for CAF-directed cancer therapeutics.