Receptor ligand-triggered resistance to alectinib and its circumvention by Hsp90 inhibition in EML4-ALK lung cancer cells
抄録
金沢大学がん進展制御研究所
Alectinib is a new generation ALK inhibitor with activity against the gatekeeper L1196M mutation that showed remarkable activity in a phase I/II study with echinoderm microtubule associated protein-like 4 (EML4) - anaplastic lymphoma kinase (ALK) non-small cell lung cancer (NSCLC) patients. However, alectinib resistance may eventually develop. Here, we found that EGFR ligands and HGF, a ligand of the MET receptor, activate EGFR and MET, respectively, as alternative pathways, and thereby induce resistance to alectinib. Additionally, the heat shock protein 90 (Hsp90) inhibitor suppressed protein expression of ALK, MET, EGFR, and AKT, and thereby induced apoptosis in EML4-ALK NSCLC cells, even in the presence of EGFR ligands or HGF. These results suggest that Hsp90 inhibitors may overcome ligand-triggered resistance to new generation ALK inhibitors and may result in more successful treatment of NSCLC patients with EML4-ALK.
収録刊行物
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- Oncotarget
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Oncotarget 5 (13), 4920-4928, 2014-01-01
Impact Journals LLC
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詳細情報 詳細情報について
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- CRID
- 1390295425029254912
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- NII論文ID
- 120005830567
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- ISSN
- 19492553
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- Web Site
- http://hdl.handle.net/2297/45905
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- IRDB
- CiNii Articles