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Molecular Cancer
Published in: Molecular Cancer 1/2018

Open Access 01-12-2018 | Review

Role of Non Receptor Tyrosine Kinases in Hematological Malignances and its Targeting by Natural Products

Authors: Kodappully S. Siveen, Kirti S. Prabhu, Iman W. Achkar, Shilpa Kuttikrishnan, Sunitha Shyam, Abdul Q. Khan, Maysaloun Merhi, Said Dermime, Shahab Uddin

Published in: Molecular Cancer | Issue 1/2018

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Abstract

Tyrosine kinases belong to a family of enzymes that mediate the movement of the phosphate group to tyrosine residues of target protein, thus transmitting signals from the cell surface to cytoplasmic proteins and the nucleus to regulate physiological processes. Non-receptor tyrosine kinases (NRTK) are a sub-group of tyrosine kinases, which can relay intracellular signals originating from extracellular receptor. NRTKs can regulate a huge array of cellular functions such as cell survival, division/propagation and adhesion, gene expression, immune response, etc. NRTKs exhibit considerable variability in their structural make up, having a shared kinase domain and commonly possessing many other domains such as SH2, SH3 which are protein-protein interacting domains. Recent studies show that NRTKs are mutated in several hematological malignancies, including lymphomas, leukemias and myelomas, leading to aberrant activation. It can be due to point mutations which are intragenic changes or by fusion of genes leading to chromosome translocation. Mutations that lead to constitutive kinase activity result in the formation of oncogenes, such as Abl, Fes, Src, etc. Therefore, specific kinase inhibitors have been sought after to target mutated kinases. A number of compounds have since been discovered, which have shown to inhibit the activity of NRTKs, which are remarkably well tolerated. This review covers the role of various NRTKs in the development of hematological cancers, including their deregulation, genetic alterations, aberrant activation and associated mutations. In addition, it also looks at the recent advances in the development of novel natural compounds that can target NRTKs and perhaps in combination with other forms of therapy can show great promise for the treatment of hematological malignancies.
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Metadata
Title
Role of Non Receptor Tyrosine Kinases in Hematological Malignances and its Targeting by Natural Products
Authors
Kodappully S. Siveen
Kirti S. Prabhu
Iman W. Achkar
Shilpa Kuttikrishnan
Sunitha Shyam
Abdul Q. Khan
Maysaloun Merhi
Said Dermime
Shahab Uddin
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2018
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/s12943-018-0788-y

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