Lurasidone Sensitizes Cancer Cells to Osimertinib by Inducing Autophagy and Reduction of Survivin

Anticancer Res. 2021 Sep;41(9):4321-4331. doi: 10.21873/anticanres.15237. Epub 2021 Sep 1.


Background/aim: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are key drugs in cancer treatment due to their minor adverse effects and outstanding anticancer effects. However, drugs for overcoming EGFR-TKI resistance are not in clinical use so far. Therefore, to overcome resistance, we focused on lurasidone, a new antipsychotic drug, due to its mild adverse effect profile from the viewpoint of drug repositioning.

Materials and methods: We explored the effects of lurasidone alone or in combination with EGFR-TKI on the growth of osimertinib-resistant cancer cells the anti-apoptotic marker expression such as survivin, and autophagy levels by LC-3B expression.

Results: Within a non-toxic concentration range in normal cells, lurasidone and osimertinib combination therapy showed a growth-inhibitory effect in osimertinib-resistant cancer cells in vitro and in vivo. Furthermore, lurasidone decreased survivin expression and mildly induced autophagy.

Conclusion: Lurasidone may increase the sensitivity to osimertinib in osimertinib-resistant cancer cells in drug repurposing.

Keywords: Drug repositioning; autophagy; chemotherapy; drug resistance; mental illnesses; osimertinib; survivin.

MeSH terms

  • A549 Cells
  • Acrylamides / administration & dosage*
  • Acrylamides / pharmacology
  • Aniline Compounds / administration & dosage*
  • Aniline Compounds / pharmacology
  • Animals
  • Autophagy / drug effects
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Down-Regulation
  • Drug Resistance, Neoplasm / drug effects*
  • Drug Synergism
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism
  • Lurasidone Hydrochloride / administration & dosage*
  • Lurasidone Hydrochloride / pharmacology
  • Mice
  • Microtubule-Associated Proteins / metabolism
  • Survivin / metabolism*
  • Xenograft Model Antitumor Assays


  • Acrylamides
  • Aniline Compounds
  • BIRC5 protein, human
  • MAP1LC3B protein, human
  • Microtubule-Associated Proteins
  • Survivin
  • osimertinib
  • Lurasidone Hydrochloride