Chapter 3 Kinase Inhibitors

Publication date: 2017
Source:Adverse Events and Oncotargeted Kinase Inhibitors
Author(s): Giuseppe Tridente
The fundamental characteristics of cancer are self-sufficiency of proliferative signals, insensitivity to antigrowth signals, resistance to cell death induction (including apoptosis), limitless replicative potential, sustained angiogenesis, and capacity of tissue invasion/metastasis. All these functional aspects are largely under the control of kinases and their typical phosphorylation mechanism. The overall tumor capability is sustained by a network of pathways, intracellular cross talk subcircuits, and a series of extracellular stimuli derived not only from the transformed cell population, but also from normal tissue components that contribute to modulate tumor progression. An additional and unique condition that also characterizes malignant cells is the addiction to a single signal pathway, which turns into an advantage for targeted inhibition. On this basis, a number of kinase inhibitors have been developed with the aim of interfering with vital signs that preferably lead to neoplastic growth, as well as signaling pathways that support tumor survival and adaptation to host environment. After fundamental preliminary investigation, the discovery of imatinib, directed against the BCR-ABL oncogenic kinase protein, opened an enthusiastic search for a number of kinase inhibitors directed to various kinase members, which rapidly and successfully reached the clinical level. The chapter deals with general characteristics and classification criteria of these powerful drugs and in particular with mechanistic aspects related to their pharmacologic activity and potential capacity of induction of adverse events.



http://ift.tt/2r0ayVn