Nanoformulations of small molecule protein tyrosine kinases inhibitors potentiate targeted cancer therapy

Int J Pharm. 2020 Jan 5:573:118785. doi: 10.1016/j.ijpharm.2019.118785. Epub 2019 Oct 31.

Abstract

Protein tyrosine kinases (PTKs) are closely related to tumor development and usually participate in apoptosis, DNA repair, and cell proliferation by activating signaling pathways. Therefore, PTKs have become the most promising targets for cancer therapy. In recent years, a large number of studies on the mechanism of tyrosine kinase activation have indicated that tyrosine kinase inhibitors (TKIs) have important clinical significance and application prospects as targeted anticancer drugs because they can effectively block certain cellular signaling pathways, inhibit tumor metastases and reduce tumor proliferation. Although the increasing emergence of anticancer drug resistance limits the clinical application of TKIs, emerging nanotechnology has made it possible to solve this problem. In this work, the state-of-art of small molecule protein tyrosine kinase inhibitors and the applications of drug delivery systems for TKIs are reviewed, and the potentials and challenges for future research of small molecule TKIs are addressed.

Keywords: Combination therapeutic strategies; Drug resistance; Signaling pathways; Small molecule tyrosine kinase inhibitors; Targeted delivery.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / pharmacology
  • Drug Delivery Systems
  • Drug Resistance, Neoplasm
  • Humans
  • Molecular Targeted Therapy
  • Neoplasms / drug therapy*
  • Neoplasms / enzymology
  • Protein Kinase Inhibitors / administration & dosage*
  • Protein Kinase Inhibitors / pharmacology
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Signal Transduction

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Protein-Tyrosine Kinases