Basic research at IRCC is mainly focused on identifying and characterizing the multifaceted molecular mechanisms responsible for neoplastic cell invasive behavior. Indeed, lethality of most malignant tumors is due to the acquired ability of cancer cells to dedifferentiate and invade neighboring tissues, blood and lymphatic vessels, finally colonizing and impairing the function of vital organs, such as liver, lungs and central nervous system.
Over the last 15 years, IRCC scientists unveiled the molecular details of several key aspects of cancer invasion. Historically interested in investigating the pro-metastatic role of the tyrosine kinase receptor Met, in recent times they found that tumor hypoxia can promote the expression and activation of Met, finally promoting cancer cell invasion. Presently, they are investigating the mechanisms leading to transformation and drug sensitivity in Met-addicted tumors. They also identified Plexins, a class of Met-related membrane proteins, as semaphorin receptors and integrins as one of their major signaling targets. Furthermore, they provided compelling evidence that different semaphorins can be important regulators of tumor angiogenesis, inflammation, and metastatization as well. Very recently, they uncovered that vascular endothelial and smooth muscle cells express the synaptic surface proteins Neurexins and Neuroligins, which behave as angiogenesis regulators.
Terrific results have been reached by studying the role of the combined effects of somatic mutations in determining the resistance to targeted therapies. The use of knock-in cell lines, in which the expression of each oncogenic mutation is under the control of the corresponding endogenous promoter, together the analysis of human series allowed discovering that KRAS mutations render colon-cancer tumors insensitive to the therapies with monoclonal antibodies anti-EGFR.
Finally IRCC scientists are generating transcriptomic, miRNAomic and proteomic signatures to define new diagnostic classifiers.
The ongoing basic research at IRCC is devoted at further studying the role of these and other newly identified molecular players and cellular processes, such as traffic and metabolism, in the regulation of cancer growth and metastatic dissemination. To reach this goal the different units participate to two different flexible and dynamics programs: Molecular Pathology and Tumor-Microenvironment interaction. |
