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

Abstract

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.

• Authors: Shuhei Suzuki, Masahiro Yamamoto, Tomomi Sanomachi, Keita Togashi, Shizuka Seino, Asuka Sugai, Takashi Yoshioka, Masashi Okada, Chifumi Kitanaka
• Journal: Anticancer research (Anticancer Res) Vol. 41 Issue 9 Pg. 4321-4331 (Sep 2021) ISSN: 1791-7530 [Electronic] Greece
• PMID: 34475052 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Chemical References

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

Topics

• A549 Cells
• Acrylamides (administration & dosage, pharmacology)
• Aniline Compounds (administration & dosage, pharmacology)
• Animals
• Autophagy (drug effects)
• Carcinoma, Non-Small-Cell Lung (drug therapy, 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, metabolism)
• Lurasidone Hydrochloride (administration & dosage, pharmacology)
• Mice
• Microtubule-Associated Proteins (metabolism)
• Survivin (metabolism)
• Xenograft Model Antitumor Assays