Heat Shock Protein 90 Inhibitors in Lung Cancer Therapy

  • Suman Chatterjee
  • Timothy F. BurnsEmail author
Part of the Heat Shock Proteins book series (HESP, volume 17)


Heat shock protein 90 (HSP90) plays crucial roles in intracellular quality control mechanisms leading to cytoprotection against variety of stressors including hypoxia, oxidative and thermal and oncogenic stress. The chaperoning activity of the evolutionary conserved and ubiquitously expressed HSP90 is adenosine triphosphate (ATP)–dependent and is essential for the folding, maturation, stabilization, activation or proteolytic degradation of its diverse array of client proteins, many of which are products of driver oncogenes in multiple cancers. Hence, tumorigenesis regulation by HSP90 chaperonage function has been the subject of extensive investigation for decades. Targeted HSP90 inhibition has shown promise and may provide an effective and alternate therapeutic approach to treat patients with lung cancer, especially non-small cell lung cancer (NSCLC) with specific mutational background or that have been characterized to show acquired resistance to other drugs targeting different signaling proteins. Although development of HSP90 inhibitors has spanned decades, both preclinically and clinically, the promise is far from being reached. In this chapter, we discuss the potential of HSP90 inhibition, and the preclinical and clinical development and future of important HSP90 small molecule inhibitors that have been or will be critical for lung cancer therapeutics.


17-AAG EGFR Ganetespib HSP90 KRAS Lung cancer NSCLC 





adenosine diphosphate


adenosine triphosphate


C-terminal domain


epidermal growth factor receptor


endoplasmic reticulum


US Food Administration




heat shock factor


heat shock protein 90


heat shock protein gene


mitogen-activated protein kinase


middle domain


next generation sequencing


non-small cell lung cancer


N-terminal domain


objective response rate


overall survival


progression free survival




reactive oxygen species


squamous cell carcinoma


tyrosine kinase inhibitor


tetratricopeptide repeat



We would like to acknowledge the LUNGevity Foundation for support of preclinical Hsp90 inhibitor studies.


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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Medicine, Division of Hematology Oncology, UPMC Hillman Cancer CenterUniversity of PittsburghPittsburghUSA

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