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

• Published in: Anticancer research Vol. 41; no. 9; pp. 4321 - 4331
• Main Authors: Suzuki, Shuhei, Yamamoto, Masahiro, Sanomachi, Tomomi, Togashi, Keita, Seino, Shizuka, Sugai, Asuka, Yoshioka, Takashi, Okada, Masashi, Kitanaka, Chifumi
• Format: Journal Article
• Language: English
• Published: Greece International Institute of Anticancer Research 01.09.2021
• Subjects: A549 Cells; Acrylamides - administration & dosage; Acrylamides - pharmacology; Aniline Compounds - administration & dosage; Aniline Compounds - pharmacology; Animals; Anticancer properties; Antipsychotics; Apoptosis; Autophagy; Autophagy - drug effects; Biocompatibility; Cancer; Cancer therapies; 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; Drug Resistance, Neoplasm - drug effects; Drug Synergism; Drugs; Epidermal growth factor; Epidermal growth factor receptors; Gene Expression Regulation, Neoplastic - drug effects; Growth factors; Humans; Kinases; Lung Neoplasms - drug therapy; Lung Neoplasms - metabolism; Lurasidone Hydrochloride - administration & dosage; Lurasidone Hydrochloride - pharmacology; Mice; Microtubule-Associated Proteins - metabolism; Phagocytosis; Protein-tyrosine kinase receptors; Side effects; Survival; Survivin; Survivin - metabolism; Targeted cancer therapy; Tyrosine; Xenograft Model Antitumor Assays; survivin; autophagy; osimertinib; Drug repositioning; mental illnesses; drug resistance; chemotherapy
• ISSN: 0250-7005; 1791-7530
• DOI: 10.21873/anticanres.15237

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