Heat shock protein antagonists in early stage clinical trials for NSCLC

Lizza E.L. Hendriks, Anne Marie C. Dingemans*

*Corresponding author for this work

Research output: Contribution to journalReview articleAcademicpeer-review

50 Citations (Scopus)
13 Downloads (Pure)

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 languageEnglish
Pages (from-to)541-550
Number of pages10
JournalExpert Opinion on Investigational Drugs
Volume26
Issue number5
DOIs
Publication statusPublished - May 2017
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2017 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

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