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Targeted Oncology

, Volume 13, Issue 4, pp 423–436 | Cite as

MicroRNAs as Mediators of Resistance Mechanisms to Small-Molecule Tyrosine Kinase Inhibitors in Solid Tumours

  • Michele Ghidini
  • Jens C. Hahne
  • Melissa Frizziero
  • Gianluca Tomasello
  • Francesco Trevisani
  • Andrea Lampis
  • Rodolfo Passalacqua
  • Nicola Valeri
Review Article

Abstract

Receptor tyrosine kinases (RTKs) are widely expressed transmembrane proteins that act as receptors for growth factors and other extracellular signalling molecules. Upon ligand binding, RTKs activate intracellular signalling cascades, and as such are involved in a broad variety of cellular functions including differentiation, proliferation, migration, invasion, angiogenesis, and survival under physiological as well as pathological conditions. Aberrant RTK activation can lead to benign proliferative conditions as well as to various forms of cancer. Indeed, more than 70% of the known oncogene and proto-oncogene transcripts involved in cancer code for RTKs. Consequently, these receptors are broadly studied as targets in the treatment of different tumours, and a large variety of small-molecule tyrosine kinase inhibitors (TKIs) are approved for therapy. In most cases, patients develop resistance to the TKIs within a short time. MicroRNAs are short (18–22 nucleotides) non-protein-coding RNAs that fine-tune cell homeostasis by controlling gene expression at the post-transcriptional level. Deregulation of microRNAs is common in many cancers, and increasing evidence exists for an important role of microRNAs in the development of resistance to therapies, including TKIs. In this review we focus on the role of microRNAs in mediating resistance to small-molecule TKIs in solid tumours.

Notes

Acknowledgements

The authors would like to thank Ms. Kate Eason very much for her great help and support during the preparation of this manuscript, especially for language editing.

Compliance with Ethical Standards

Funding

No external funding was used in the preparation of this manuscript.

Conflict of Interest

Michele Ghidini, Jens C. Hahne, Melissa Frizziero, Gianluca Tomasello, Francesco Trevisani, Andrea Lampis, Rodolfo Passalacqua, and Nicola Valeri declare that they have no conflicts of interest that might be relevant to the contents of this manuscript.

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Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.Medical Department, Division of Oncology, ASST di CremonaOspedale di CremonaCremonaItaly
  2. 2.Centre for Molecular PathologyThe Institute of Cancer ResearchSuttonUK
  3. 3.Department of Medical OncologyThe Christie NHS Foundation TrustManchesterUK
  4. 4.Division of Experimental OncologyIRCCS San Raffaele Scientific InstituteMilanItaly
  5. 5.The Royal Marsden NHS Foundation TrustLondonUK

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