After 60 years from the first report of an enzymatic phosphorylation of proteins, protein kinases are well-established key signaling molecules that impact all major biological processes (reviewed in [1, 2]). Protein and lipid kinases fulfill essential roles in many signaling pathways that regulate normal cell functions [1–5]. Deregulation of kinase activities leads to a variety of pathologies ranging from cancer to inflammatory diseases, diabetes, infectious diseases, cardiovascular disorders, and cell growth and survival [1, 2, 5–11]. A much larger proportion of additional kinases are present in parasites and bacterial, fungal, and viral genomes that are susceptible to exploitation as drug targets . Since many human diseases result from overactivation of protein and lipid kinases due to mutations and/or overexpression, this enzyme class represents an important target for the pharmaceutical industry . Approximately one-third of all protein targets under investigation in the pharmaceutical industry are protein or lipid kinases and to date 33 small molecular weight kinase inhibitors (SMWKIs) and a handful of therapeutic antibodies have been approved for various indications mainly in oncology and many more in various stages of clinical and preclinical development . Kinase inhibitor drugs, which are in clinical trials, target all stages of signal transduction from the receptor protein tyrosine kinases that initiate intracellular signaling, through second-messenger dependent lipid and protein kinases and protein kinases that regulate the cell cycle [10, 13]. While treating chronic phase CML (an almost monogenic disease) with imatinib has been very successful, the treatment of more advanced cancers with kinase inhibitors has proven more difficult due to the heterogeneity of these cancer types as well as due to kinase inhibitor resistance resulting from selection for mutant alleles and/or upregulation of alternative signaling pathways [5, 10].
|Data di pubblicazione:||2015|
|Titolo:||Phosphorylation, Signaling, and Cancer: Targets and Targeting|
|Autori:||Marmiroli, Sandra; Fabbro, Doriano; Miyata, Yoshihiko; Pierobon, Mariaelena; Ruzzene, Maria|
|Digital Object Identifier (DOI):||10.1155/2015/601543|
|Appare nelle tipologie:||Articolo su rivista|
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