Title:MET and ALK as Targets for the Treatment of NSCLC
VOLUME: 20 ISSUE: 24
Author(s):Capelletti M, Gelsomino F. and Tiseo M.
Affiliation:Medical Oncology Unit, University Hospital of Parma, Via Gramsci 14, 43100 Parma, Italy.
Keywords:NSCLC; hepatocyte growth factor; MET; ALK rearrangements; EML4-ALK gene; kinase inhibitors; targeted therapies.
Abstract:Cell proliferation, survival, differentiation, migration and metabolism are some of the fundamental cellular processes tightly
controlled by the activity of tyrosine-kinase receptors (RTKs). The aberrant signaling of RTKs contributes to cancer growth and survival
and has become important target for therapeutic approaches. Well-characterized kinase molecular target in lung cancer, in particular in
non-small cell lung cancer (NSCLC), is the activated epidermal growth factor receptor (EGFR) pathway. More recently, the oncogenic
role of other two tyrosine-kinases, the hepatocyte growth factor receptor (MET) and the anaplastic lymphoma kinase (ALK), has been
recognized. Many different therapeutic strategies have been investigated with the goal to inhibit these receptors, subsequent downstream
signaling cascades and arrest tumor growth. This review will discuss the MET and ALK pathways, the different strategies of their inhibition
and the potential approaches to overcome acquired resistance to kinase inhibitors in these two genes.
