Preclinical and clinical evaluation of MET functions in cancer cells and in the tumor stroma

A lot of attention has been dedicated to investigate the role of the tyrosine kinase receptor MET in tumors. The acquired notion that cancer cells from different histological origin strictly rely on the engagement of this specific oncogene for their growth and survival has certainly justified the development and the use of MET-targeted therapies in the clinic. However, the function and involvement of this pathway in the stroma (that often constitutes >50% of the global cellularity of the tumor) may offer the opportunity to conceive new patient stratification criteria, rational drug design and guided trials of new combination treatments. In this review, we will summarize and discuss the role of MET in cancer cells but especially in different stromal compartments, in light of the results showed by past and recent preclinical and clinical trials with anti-MET drugs.