Abstract
Introduction:
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.
Original language | English |
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Pages (from-to) | 541-550 |
Number of pages | 10 |
Journal | Expert Opinion on Investigational Drugs |
Volume | 26 |
Issue number | 5 |
DOIs | |
Publication status | Published - May 2017 |
Externally published | Yes |
Bibliographical note
Publisher Copyright:© 2017 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.