Tumor microenvironment plasticity and heterogeneity (TMHet)

Problem 

Tumors are not composed only by tumor cells, but also include a complex and heterogeneous tumor microenvironment (TME), where immune cells, endothelial cells, fibroblasts and extracellular matrix (ECM) interact each others and support tumor growth and metastasis. Therefore, there is an urgent need to develop novel therapeutic strategies aimed at targeting not only tumor cells but also the complexity of its TME.   

Approach

With our research we aim at investigating the functional role, plasticity and heterogenity of the TME in solid tumors characterized by exacerbated desmoplastic stroma, with accumulation of cancer-associated fibroblasts (CAF) and extracellular matrix. Because of their assumed pro-tumorigenic functions, CAFs have long been considered an attractive therapeutic target. However, how CAFs change dynamically as cancers evolve, and how this may affect the overall tumour heterogeneity, remains unaddressed. To investigate these aspects of the disease, we employ in vitro and in vivo experimental models of liver tumors and metastasis and we integrate our research with high throughput transcriptomics and bioinformatic analysis.

Impact

While dissecting the TME complexity may represent a therapeutic opportunity towards the development of new targeted therapies, a more extensive understanding of the CAFs and tumour stroma is urgently needed to guarantee a successful targeting and avoid deleterious outcomes in patients.   

With our experience in CAF research, with our research line, we aim to decipher, analyze, and model the heterogeneity and plasticity of CAFs for their use in future combination therapies for the treatment of desmoplastic tumors.