TY - JOUR T1 - Ganetespib in Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor-resistant Non-small Cell Lung Cancer JF - Anticancer Research JO - Anticancer Res SP - 1767 LP - 1775 DO - 10.21873/anticanres.13283 VL - 39 IS - 4 AU - EISUKE KURIHARA AU - KAZUHIKO SHIEN AU - HIDEJIRO TORIGOE AU - TATSUAKI TAKEDA AU - YUTA TAKAHASHI AU - YUSUKE OGOSHI AU - TAKAHIRO YOSHIOKA AU - KEI NAMBA AU - HIROKI SATO AU - KEN SUZAWA AU - HIROMASA YAMAMOTO AU - JUNICHI SOH AU - MIKIO OKAZAKI AU - TADAHIKO SHIEN AU - SHUTA TOMIDA AU - SHINICHI TOYOOKA Y1 - 2019/04/01 UR - http://ar.iiarjournals.org/content/39/4/1767.abstract N2 - Background: The 90-kDa heat-shock protein (HSP90) is a chaperone protein expressed at high levels in cancer cells and is involved in the folding or stabilization of several client proteins, including epidermal growth factor receptor (EGFR). Ganetespib is a second-generation HSP90 inhibitor with a potent antitumor effect against various cancer types. Materials and Methods: This study examined the antitumor effect of ganetespib in EGFR-mutant non-small cell lung cancer (NSCLC) cells and experimentally established EGFR-tyrosine kinase inhibitor (TKI)-resistant cells harboring various resistance mechanisms, including EGFR T790M mutation, met proto-oncogene amplification, and epithelial–mesenchymal transition. Results: Ganetespib showed a potent antitumor effect at low concentrations, suppressing EGFR-related downstream pathway molecules and inducing cleavage of poly ADP-ribose polymerase in all examined EGFR-TKI-resistant cell lines in vitro. Ganetespib also inhibited in vivo tumor growth in resistant cells harboring EGFR T790M. Conclusion: Ganetespib might be a promising therapeutic option for the treatment of patients with EGFR-TKI-resistant NSCLC. ER -