Cancer is a very deadly disease with more than 3,000,000 new cases diagnosed every year only in the EU (2012 estimates from IARC). Despite the progresses made in the last years, only a minority of selected patients benefit from the molecularly targeted agents, while the vast majority (including relapsing patients) are treated with conventional cytotoxic chemotherapy. There is therefore an urgent need for the identification of novel fundamental mechanisms of cancer biology and chemoresistance in order to develop more effective drugs and therapeutic strategies.
The recent discovery of epithelial-to-mesenchymal transition (EMT), cancer stem cells (CSCs) and of their functional association and interdependence represent some of the most promising advances in the last two decades of cancer research. CSCs are defined as a subpopulation of undifferentiated cancer cells with stem-like features responsible for tumors’ heterogeneity and for some of the most lethal features of cancers: tumorigenicity, metastatic spread, relapse and chemoresistance. The inter-conversion between CSCs and non-CSCs has been recently reported and the EMT clearly functionally involved. The EMT is a de-differentiation process frequently observed in cancers with increased invasive potential and drug resistance. A recently emerging concept is that the plasticity of cancers is greater than what initially hypothesized, and therefore a better understanding of the mechanisms behind the inter-conversion of cancer cells between differentiation stages may have many therapeutic implications.
The Junior Group aims at identifying novel (fundamental) mechanisms and molecular determinants that regulate the plasticity of cancer and at studying the association between cancer differentiation and sensitivity to chemotherapy, by the use of several cell and molecular biology techniques, mouse models, and the analysis of human samples as well as by –omics and high-throughput approaches.