ArticleTranslational lung cancer research2019
Hsp90 inhibitors enhance the antitumoral effect of osimertinib in parental and osimertinib-resistant non-small cell lung cancer cell lines.
Article in Translational lung cancer research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.
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Who cites it
9 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.
- Therapeutic exploration of uncommon EGFR exon 20 insertion mutations in advanced non-small cell lung cancer: breaking through brambles and thorns.Journal of cancer research and clinical oncology · 2022Pooled it
- Erlotinib and Onalespib Lactate Focused on EGFR Exon 20 Insertion Non-Small Cell Lung Cancer (NSCLC): A California Cancer Consortium Phase I/II Trial (NCI 9878).Clinical lung cancer · 2021Trial
- Comprehensive Analysis of Cuproptosis-Related Genes According to Cancer Stage and Their Prognostic Value in Cervical Cancer.International journal of molecular sciences · 2026Article
- Heat shock proteins as hallmarks of cancer: insights from molecular mechanisms to therapeutic strategies.Journal of hematology & oncology · 2024Review
- Article
- Anti-EGF nanobodies enhance the antitumoral effect of osimertinib and overcome resistance in non-small cell lung cancer (NSCLC) cellular models.Medical oncology (Northwood, London, England) · 2022Article
- Hsp90 up-regulates PD-L1 to promote HPV-positive cervical cancer via HER2/PI3K/AKT pathway.Molecular medicine (Cambridge, Mass.) · 2021Article
- HSP90 inhibition overcomes EGFR amplification-induced resistance to third-generation EGFR-TKIs.Thoracic cancer · 2021Article
- Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundOsimertinib improve therapy for non-small cell lung cancer (NSCLC). However, invariable acquired resistance appears.
methodsMTT assay was used to analyze cell viability. Protein expression and activation was detected by Western blotting. In addition, the effects of heat shock protein 90 (Hsp90) inhibitors and osimertinib were studied in colony formation assays.
resultsOur laboratory generated osimertinib resistant cell lines from PC9 cell line and overexpression or activation of several proteins was detected. Hsp90 inhibitors, ganetespib and luminespib, inhibited cell viability and colony formation in H1975, PC9 and PC9-derived osimertinib-resistant cell lines and combination of these inhibitors with osimertinib achieved to enhance this cell viability and colony formation inhibition. Luminespib downregulated the expression of the several proteins involved in osimertinib-resistance and the combination of this compound plus osimertinib caused an important decrease of expression of several of these proteins, such as Stat3, Yap, Akt, EGFR and Met. Osimertinib activated the phosphorylation of several membrane receptors and downstream molecules that was partially inhibited by luminespib. In addition, a lung cancer patient with an EGFR eon 20 mutation had a partial radiographic response to ganetespib.
conclusionsHsp90 inhibitors and osimertinib exhibits a good efficiency to inhibit cell viability, colony formation and inhibits expression and activation of proteins involved in osimertinib-resistance and may represent an effective strategy for NSCLC with intrinsic resistance to osimertinib inhibition.
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