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Front. Pharmacol. | doi: 10.3389/fphar.2019.01011

Src tyrosine kinase inhibitors: New perspectives on their immune-, antiviral and seno-therapeutic potential

  • 1Universidad Europea de Madrid, Spain

Src is the prototypical member of a large family of non-receptor protein-tyrosine kinases. Aberrant and altered expression of these tyrosine kinases has been extensively reviewed in the literature and shown to be involved in a plethora of key cellular processes leading to tumor development and progression. Therefore, Src tyrosine kinases have been considered an essential target for drug development to fight tumor malignancies. Since the approval, by FDA in 2001, of the first Src tyrosine kinase inhibitor (STKI) Imatinib for the treatment of chronic myeloid leukemia (CML), the number of these inhibitors has increased notably, Dasatinib being the most widely studied.
STKIs generally act by reducing or stopping the aberrant activity of several tyrosine-kinase family members in tumor cells. A decade ago, scientific evidence pointed to the existence of alternative mechanisms involving key immune cells of the tumor microenvironment (cytotoxic T lymphocytes and NK). Paradoxically, in addition to a well-known immunosuppressive effect preventing T lymphocyte activation, the reported increase in monoclonal and oligoclonal large granular lymphocytosis in a group of Dasatinib-treated patients reduced susceptibility to opportunistic infections and improved the prognosis of CML patients receiving the drug.
Herein we review the recent findings on the immunomodulatory properties of STKIs, including the promising role of γδ T-lymphocytes, and their plausible interest in the clinic. Moreover, we will briefly summarize potential benefits, adverse effects and safety concerns regarding viral infections, as well as the ability of STKIs to alleviate age-associated physical dysfunction and their impact.

Keywords: STK inhibitor, Dasatinib, Immunotherapy, LGL cells, Gamma Delta (γδ) T cells, Senolytic, Progeria

Received: 18 Mar 2019; Accepted: 08 Aug 2019.

Copyright: © 2019 Rivera-Torres and San Jose. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Dr. José Rivera-Torres, Universidad Europea de Madrid, Villaviciosa de Odón, 28670, Madrid, Spain,
Dr. Esther San Jose, Universidad Europea de Madrid, Villaviciosa de Odón, 28670, Madrid, Spain,