Oncotarget

Reviews:

Tyrosine kinase inhibitors and mesenchymal stromal cells: effects on self-renewal, commitment and functions

Adriana Borriello _, Ilaria Caldarelli, Debora Bencivenga, Emanuela Stampone, Silverio Perrotta, Adriana Oliva and Fulvio Della Ragione

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Oncotarget. 2017; 8:5540-5565. https://doi.org/10.18632/oncotarget.12649

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Abstract

Adriana Borriello1, Ilaria Caldarelli1, Debora Bencivenga1, Emanuela Stampone1, Silverio Perrotta2, Adriana Oliva1 and Fulvio Della Ragione1

1 Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples, Italy

2 Department of Woman, Child and of General and Specialized Surgery, Second University of Naples, Naples, Italy

Correspondence to:

Fulvio Della Ragione, email:

Adriana Borriello, email:

Keywords: tyrosine kinase inhibitors, target therapy, mesenchymal stromal cells, bone marrow milieu, osteogenesis

Received: July 28, 2016 Accepted: October 04, 2016 Published: October 13, 2016

Abstract

The hope of selectively targeting cancer cells by therapy and eradicating definitively malignancies is based on the identification of pathways or metabolisms that clearly distinguish “normal” from “transformed” phenotypes. Some tyrosine kinase activities, specifically unregulated and potently activated in malignant cells, might represent important targets of therapy. Consequently, tyrosine kinase inhibitors (TKIs) might be thought as the “vanguard” of molecularly targeted therapy for human neoplasias. Imatinib and the successive generations of inhibitors of Bcr-Abl1 kinase, represent the major successful examples of TKI use in cancer treatment. Other tyrosine kinases have been selected as targets of therapy, but the efficacy of their inhibition, although evident, is less definite. Two major negative effects exist in this therapeutic strategy and are linked to the specificity of the drugs and to the role of the targeted kinase in non-malignant cells. In this review, we will discuss the data available on the TKIs effects on the metabolism and functions of mesenchymal stromal cells (MSCs). MSCs are widely distributed in human tissues and play key physiological roles; nevertheless, they might be responsible for important pathologies. At present, bone marrow (BM) MSCs have been studied in greater detail, for both embryological origins and functions. The available data are evocative of an unexpected degree of complexity and heterogeneity of BM-MSCs. It is conceivable that this grade of intricacy occurs also in MSCs of other organs. Therefore, in perspective, the negative effects of TKIs on MSCs might represent a critical problem in long-term cancer therapies based on such inhibitors.


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