Background
Cancer is a multistep process that results from the progressive accumulation of mutations which either inactivate tumor suppressor genes or activate dominant proto-oncogenes. These aberrant events free cells from proliferative control and allow primary tumor formation. The initial tumor growth is followed by metastatic spread. “Invasive growth” defines the ability of neoplastic cells to invade the adjacent tissues, survive in foreign compartments and proliferate to settle at distant sites. Invasive growth and metastasis formation are the main cause of death from cancer. Therefore therapeutic approaches aiming at blocking the metastatic spread are strongly required.
Moreover it has been shown that mutations accumulated by a cancer cell during tumor progression are not equivalent; they have different strength and roles. Some mutations are more potent than others and become the driving force for tumor initiation and progression. Cancer cells become exclusively dependent from the activity of those mutated genes for their growth and survival. This concept is known as “oncogene addiction”. As tumoral cells depend on the aberrant activity of a specific mutated gene to survive and proliferate, it is virtually sufficient to inactivate that gene to induce growth arrest and provoke cell death (apoptosis). Many genes able to induce oncogene addiction codify molecules involved in generation and transduction of signaling originated from growth factors; among them a key role is played by tyrosine kinase receptors
Achievements
In this contest the Exploratory Research Laboratory focuses on genes belonging to the tyrosine kinase receptor family. In the last years targeted therapies designed at specifically silencing members of this family has proven to be winning and a large cohort of patients benefits from therapies designed at silencing kinase receptors where aberrantly regulated. Targets currently investigated in our Laboratory are RON (a tyrosine kinase receptor belonging to the Scatter Factor Receptor subfamily), orphan receptors RORs and tyrosine kinase Axl (member of the TAM subfamily).
Goals
The mission of the Exploratory Research Laboratory is to explore the role of less studied tyrosine kinase receptors in tumor progression and orchestration of the metastatic spread. The research and validation of new therapeutic targets, together with the creation of molecules designed to specifically inhibit them, is vital to fight cancer particularly in a more general contest in which several proteins/receptors are attacked at the same time in an initial massive assault against the tumor.
