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Tyrosine kinase inhibitors and their unique therapeutic potentialities to combat cancer

Y. Zhao, M. Bilal, A. Raza, MI. Khan, S. Mehmood, U. Hayat, STS. Hassan, HMN. Iqbal

. 2021 ; 168 (-) : 22-37. [pub] 20201205

Language English Country Netherlands

Document type Journal Article, Review

Persistent link   https://www.medvik.cz/link/bmc21019393

Cancer is one of the leading causes of death with a mortality rate of 12%. Although significant progress has been achieved in cancer research, the effective treatment of cancer remains the greatest global challenge in medicine. Dysregulation of tyrosine kinases (TK) is one of the characteristics of several types of cancers. Thus, drugs that target and inhibit these enzymes, known as TK inhibitors (TKIs), are considered vital chemotherapeutics to combat various types of cancer. The oral bioavailability of available TKIs and their targeted therapy are their potential benefits. Based on these characteristics, most TKIs are included in first/second-line therapy for the treatment of different cancers. This review aims to shed light on orally-active TKIs (natural and synthetic molecules) and their promising implication in the therapy of numerous types of tumors along with their mechanisms of action. Further, recent progress in the development of synthetic and isolation of natural TKIs is reviewed. A significant growth in research regarding the development of new-generation TKIs is made with time (23 FDA-approved TKIs from 2018) due to their better therapeutic response. Oral bioavailability should be considered as an important parameter while developing of new-generation TKIs; however, drug delivery systems can also be used to address issue of poor bioavailability to a certain extent. Moreover, clinical trials should be designed in consideration of the development of resistance and tumor heterogeneity.

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$a Bilal, Muhammad $u School of Life Science and Food Engineering, Huaiyin Institute of Technology, Huaian 223003, China. Electronic address: bilaluaf@hotmail.com
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$a Raza, Ali $u School of Biomedical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China
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$a Khan, Muhammad Imran $u Hefei National Lab for Physical Sciences at the Microscale and the Centers for Biomedical Engineering, University of Science and Technology of China, Hefei, Anhui 230027, China
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$a Mehmood, Shahid $u Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
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$a Hayat, Uzma $u School of Biomedical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China
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$a Iqbal, Hafiz M N $u Tecnologico de Monterrey, School of Engineering and Sciences, Monterrey, 64849, Mexico. Electronic address: hafiz.iqbal@tec.mx
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