Journal
CANCERS
Volume 12, Issue 6, Pages -Publisher
MDPI
DOI: 10.3390/cancers12061448
Keywords
Src; src family tyrosine kinases; cancer metastasization; cancer migration; cancer invasion; epithelial-to-mesenchymal transition; clinical trial; targeted therapy; dasatinib
Categories
Funding
- MIUR
- National Operational Program for Research and Innovation (Programma Operativo Nazionale Ricerca e Innovazione) [DOT13SR6G7]
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Src is the prototypal member of Src Family tyrosine Kinases (SFKs), a large non-receptor kinase class that controls multiple signaling pathways in animal cells. SFKs activation is necessary for the mitogenic signal from many growth factors, but also for the acquisition of migratory and invasive phenotype. Indeed, oncogenic activation of SFKs has been demonstrated to play an important role in solid cancers; promoting tumor growth and formation of distant metastases. Several drugs targeting SFKs have been developed and tested in preclinical models and many of them have successfully reached clinical use in hematologic cancers. Although in solid tumors SFKs inhibitors have consistently confirmed their ability in blocking cancer cell progression in several experimental models; their utilization in clinical trials has unveiled unexpected complications against an effective utilization in patients. In this review, we summarize basic molecular mechanisms involving SFKs in cancer spreading and metastasization; and discuss preclinical and clinical data highlighting the main challenges for their future application as therapeutic targets in solid cancer progression
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