Page 27 - IMO-2-3

Innovative Medicines & Omics

REVIEW ARTICLE
Tyrosine kinases: Structural insights and

mechanistic roles in cancer progression and
therapeutics

Eswar Kumar Nadendla * , Gangadhar P. Vadla , Manohar Radhakrishnan ,
2
1
3
1
and Raghavendra Sashi Krishna Nagampalli *
1 Department of Immunology, St Jude Children’s Research Hospital, Memphis, Tennessee,
United States of America
2 Department of Veterinary Pathobiology, Bond Life Sciences Center, Columbia, Missouri,
United States of America
3 Department of Biochemistry and Molecular Biology, Indiana University School of Medicine,
Indianapolis, Indiana, United States of America

Abstract
Protein tyrosine kinases (PTKs) are key enzymes of cellular signaling, regulating
key processes such as proliferation, differentiation, migration, metabolism, and
apoptosis. Tyrosine kinases (TKs) modulate protein functions in normal and disease
states by phosphorylation of tyrosine residues on target proteins. In this critical
*Corresponding authors: role, dysregulation of TKs is directly linked with disease progression, particularly in
Eswar Kumar Nadendla cancer, therefore making TKs an attractive target for therapeutic intervention. The
(nadenlagem@gmail.com)
Raghavendra Sashi Krishna PTK family is broadly classified into receptor TKs (RTKs) and non-receptor TKs (NRTKs),
Nagampalli having variation at both structural and functional levels. RTKs are membrane-bound
(rsnagampalli@gmail.com) kinases that initiate intracellular signaling when they react with extracellular ligands,
Citation: Nadendla EK, Vadla GP, whereas NRTKs within the cytoplasm or nucleus convey intracellular signaling upon
Radhakrishnan M, Nagampalli RSK. receptor activation. This paper aims to review the organization, mechanistic activity,
Tyrosine kinases: Structural insights and therapeutic potential of PTKs, with a particular focus on epidermal growth factor
and mechanistic roles in cancer
progression and therapeutics. Innov receptor and proto-oncogene tyrosine-protein kinase (Src) as representatives of RTK
Med Omics. 2025;2(3):21-43. and NRTK, respectively. In addition, this review also focuses on addressing emerging
doi: 10.36922/IMO025200022 strategies to enhance tyrosine kinase inhibitor efficacy and overcome acquired
Received: May 15, 2025 resistance in cancer therapy.
Revised: July 9, 2025
Accepted: July 17, 2025 Keywords: Protein tyrosine kinases; Epidermal growth factor receptor; Receptor tyrosine
kinases; Non-receptor tyrosine kinases; Cancer; Src kinase; Exo-site
Published online: August 20, 2025
Copyright: © 2025 Author(s).
This is an Open-Access article
distributed under the terms of the
Creative Commons Attribution 1. Introduction
License, permitting distribution,
and reproduction in any medium, Tyrosine kinases (TKs) are crucial enzymes involved in signal transduction that regulates
provided the original work is key cellular processes such as proliferation, differentiation, migration, metabolism, and
properly cited. apoptosis. By catalyzing the phosphorylation of tyrosine residues in target proteins,
1-3
4
Publisher’s Note: AccScience kinases mediate vital cellular communication and maintain homeostasis. Phosphorylation
Publishing remains neutral with functions as a post-translational modification that is essential for normal cellular processes,
regard to jurisdictional claims in 5
published maps and institutional but its dysregulation can cause disease, including cancer. Unusual activation of protein
affiliations. TKs (PTKs) is usually associated with disease progression and therapy resistance, while

Volume 2 Issue 3 (2025) 21 doi: 10.36922/IMO025200022