Abstract
Protein kinases are enzymes that transfer a phosphate group to the threonine, serine, or tyrosine residues of the target protein, regulating its activity. The activity of these enzymes are very important and strictly regulated in the cell as they promote cell proliferation, survival, and migration. In the case of any dysregulation of these enzymes, they can be associated with cancer initiation and progression. Small-molecule kinase inhibitors approved by the FDA for their improved clinical benefits are currently used in targeted therapy for the treatment of various cancers. So far, there are 62 FDA-approved therapeutic agents targeting different protein kinases, eight of which were approved in 2020. Today, kinase inhibitors are used as FDA approved cancer agents and newly developed ones are evaluated in clinical trials. Those protein kinase inhibitors can be grouped as growth factor receptor inhibitors, Ras/Raf/Mek inhibitors, phosphoinositide 3-kinase (PI3K) and cyclin dependent kinase inhibitors, other targets, and agents such as protein kinase c and 3 phosphoinositide-dependent kinase 1. In this chapter, these kinases, their pathways, and their inhibitors will be discussed in detail.
Highlights
Protein kinases (PKs) are enzymes that regulate the activity of a protein by adding phosphate group to specific amino acids using ATP as a resource, thereby resulting in a conformational change of that protein
The literature shows that vascular endothelial growth factor (VEGF) pathway is critical for renal cell carcinoma (RCC) initiation and progression, and vascular endothelial growth factor receptor (VEGFR) targeted tyrosine kinase inhibitors (TKIs) have been used for most favorable RCC treatment strategy
Fibroblast growth factor receptors (FGFRs), which are members of receptor tyrosine kinase can be thought as single pass membrane proteins due to the cellular membrane covering in a single region [43]
Summary
Protein kinases (PKs) are enzymes that regulate the activity of a protein by adding phosphate group to specific amino acids using ATP as a resource, thereby resulting in a conformational change of that protein They add terminal γ-phosphate group to the serine, threonine or tyrosine residues of the target proteins and this process is called phosphorylation. Phosphorylation can alter biological activities such as transcription and translation It can have inhibitory or stimulatory effect on the target. The success of imatinib had opened the door to exploration of other oncogenic kinases in other signaling pathways Those kinase inhibitors can be grouped as growth factor receptor inhibitors, Ras/Raf/Mek inhibitors, phosphoinositide 3-kinase (PI3K) and cyclin dependent kinase inhibitors, other targets and agents such as protein kinase c and 3 phosphoinositide-dependent kinase 1 (PDK1). This chapter will focus on the kinases’ role in oncogenic pathways and the kinase inhibitors targeting these pathways as a therapeutic option
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