Role of Tyrosine Kinases and their Inhibitors in Cancer Therapy: A Comprehensive Review

Abstract

Recently released Globocan-2020 report has been disclosed an increase in new cancer cases, cancer deaths, and 5-year prevalence cases worldwide. The higher percent proportions of cancer deaths as compared to their incidence percentage in Asia and Africa. Cancer is a genetic but not inheritable disease that consists of various abnormal cells. Depending upon the nature and site of availability of cells cancer can spread all over the body. These abnormal cells can grow infinitely in which tyrosine kinases (TKs) play an important role as mediators for cellular signal transduction processes during migration, metabolism, proliferation and differentiation, apoptotic cell death, etc. TKs belong to a specific family of an enzyme that catalyses the transferring of phosphate groups from ATP to selected tyrosine residues of a target protein during the biological process to maintain the homeostasis. They work in various steps of development and progression pathways of cancer by affecting signal transduction. The aberrant and deregulated functioning of TKs results in a defective signal transduction pathway which leads to abnormality in cell transformation, proliferation, and differentiation, thus the development of cancer. Since their discovery in 1990 to date, more than 90 TKs have been reported and divided into two categories receptor and non-receptor TKs. Higher expression levels of TKs paved their status of oncoprotein and thus, they provide a potential target for the development of anti-cancer therapeutics. Here, we provided updated cancer demographic status, cancer types, and available therapeutic options targeted cancer therapeutic strategies and the role of different TKs in cancers along with recently identified molecules that target TKs. Moreover, we also included the binding interactions of chemical inhibitors with TKs.

Novel 7-Deazapurine Incorporating Isatin Hybrid Compounds as Protein Kinase Inhibitors: Design, Synthesis, In Silico Studies, and Antiproliferative Evaluation

“…Kinases are enzymes that catalyze the phosphorylation of biomolecules that control complex cellular processes, such as growth, proliferation, differentiation, motility, and apoptosis [1,2]. In some cases, kinase enzymes become overactive and consequently lead to cancer.…”