Addition of apatorsen, an inhibitor of Hsp27, to first-line gemcitabine/carboplatin in advanced squamous cell lung cancer: Design of the Cedar study.

Schmid, Peter; Muthukumar, Dakshinmoorthy; Blackhall, Fiona; Lester, J.F.; Khan, Sarah; Illsley, Marianne; Adams, Joss; Garcia-Alonso, Angel; MacDonald-Smith, Carey; Lee, Siow Ming; Jacobs, Cindy; Middleton, Gary; James, Christine; Mousa, Kelly; Sarker, Shah-Jalal; Lim, Louise

doi:10.1200/jco.2015.33.15_suppl.tps8111

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“…Based on this background is the open-label phase II Cedar TM trial currently recruiting advanced squamous cell histology NSCLC patients: randomization is between first-line gemcitabine 1250 mg/m 2 day 1, 8/carboplatin AUC5 day 1 with or without apatorsen 600 mg iv weekly in a 3-weekly schedule (NCT02423590) [52]. Molecularly selected patients: apatorsen combined with erlotinib significantly enhanced antitumor effects when compared to erlotinib alone when tested in an EGFR-mutated, erlotinibresistant cell line [17].…”

Section: Apatorsen (Ogx-427)mentioning

confidence: 99%

Heat shock protein antagonists in early stage clinical trials for NSCLC

Hendriks

Dingemans

2017

Expert Opinion on Investigational Drugs

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Cancer cells have a higher need of chaperones than normal cells to prevent the toxic effects of intracellular protein misfolding and aggregation. Heat shock proteins (Hsps) belong to these chaperones; they are classified into families according to molecular size. Hsps are upregulated in many cancers and inhibition can inhibit tumor growth by destabilizing proteins necessary for tumor survival. In non-small cell lung cancer (NSCLC), there are three different Hsp antagonist classes that are in (early) clinical trials: Hsp90, Hsp70 and Hsp27 inhibitors. Areas covered: The rationale to use Hsp inhibitors in NSCLC will be summarized and phase I-III trials will be reviewed. Expert opinion: Several Hsp90 inhibitors have been tested in phase I-III trials, until now none was positive in unselected NSCLC; therefore development of AUY922, ganetespib and retaspimycin was halted. Results seem more promising in molecularly selected patients, especially in ALK-rearranged NSCLC. Hsp27 is overexpressed in squamous NSCLC and is a mechanism of chemotherapy resistance. The Hsp27 inhibitor apatorsen is now tested in squamous NSCLC. No phase II/III data are known for Hsp70 inhibitors. Combination of Hsp inhibitors with heat shock transcription factor 1 inhibitors or focal adhesion kinase inhibitors might be of interest for future trials.

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Section: Apatorsen (Ogx-427)mentioning

confidence: 99%