%0 Journal Article %A SHUHEI SUZUKI %A MASAHIRO YAMAMOTO %A TOMOMI SANOMACHI %A KEITA TOGASHI %A SHIZUKA SEINO %A ASUKA SUGAI %A TAKASHI YOSHIOKA %A MASASHI OKADA %A CHIFUMI KITANAKA %T Lurasidone Sensitizes Cancer Cells to Osimertinib by Inducing Autophagy and Reduction of Survivin %D 2021 %R 10.21873/anticanres.15237 %J Anticancer Research %P 4321-4331 %V 41 %N 9 %X 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. %U https://ar.iiarjournals.org/content/anticanres/41/9/4321.full.pdf