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Heat Shock Protein 90 in Human Diseases and Disorders pp 125–143Cite as

Role of HSP90 Inhibitors in the Treatment of Cancer

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Part of the book series: Heat Shock Proteins ((HESP,volume 19))

Abstract

The 90-kDa heat shock protein HSP90 is a member of a highly evolutionarily conserved class of molecular chaperone proteins indispensable for the development of cancer; when activated by cellular stress, HSP90 stabilizes oncogenic substrate “client” proteins involved in cellular processes that promote tumorigenesis. HSP90 inhibition attenuates this stabilization of aberrant client proteins in tumor cells, allowing for simultaneous targeting of multiple pathways involved in cancer cell survival. HSP90 inhibitors have been assessed as potential oncologic therapies in several preclinical and clinical studies. Although preclinically promising results have been measured, these results have not translated yet into major clinical efficacy. Combinations of HSP90 inhibitors with approved and investigational oncology drugs may represent further opportunities for the use of these agents in patients with cancer. This chapter reviews some of the important early clinical milestones observed in studies of first- and second-generation HSP90 inhibitors used as single agents and in combination. In the conclusion, possible reasons for the lack of therapeutic benefit in clinical studies are considered.

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Abbreviations

AE:

Adverse event

ALK:

Anaplastic lymphoma kinase

BRAF:

Serine/threonine-protein kinases B-Raf

CDK:

Cyclin-dependent kinase

CRAF:

Serine/threonine-protein kinases C-Raf

CRC:

Colorectal carcinoma

DLT:

Dose-limiting toxicity

EGFR:

Epidermal growth factor receptor

EMT:

Epithelial-to-mesenchymal transition

GDNF:

Glial cell line-derived neurotrophic factor

HER2:

Human epidermal growth factor receptor 2

HGF:

Hepatocyte growth factor

HSP:

Heat shock protein

HSP90:

Heat shock protein 90

MBC:

Metastatic breast cancer

MTD:

Maximum tolerated dose

NSCLC:

Non-small cell lung cancer

ORR:

Overall response rate

TNBC:

Triple-negative breast cancer

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Acknowledgements

Special thanks to Sarah Miller, PhD.

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Author notes

  1. Authors Geraldine O’Sullivan Coyne and Cecilia Monge have equally contributed to this chapter.

Authors and Affiliations

  1. Division of Cancer Treatment and Diagnosis and Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    Geraldine O’Sullivan Coyne, Cecilia Monge & Alice P. Chen

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  1. Geraldine O’Sullivan Coyne
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  2. Cecilia Monge
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  3. Alice P. Chen
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Correspondence to Alice P. Chen .

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Editors and Affiliations

  1. Department of Medicine and Director, Precision Therapeutics Proteogenomics Diagnostic Center, Eleanor N. Dana Cancer Center, University of Toledo, College of Medicine and Life Sciences, Toledo, OH, USA

    Alexzander A. A. Asea

  2. Department of Experimental Radiation Oncology, MD Anderson Cancer Center, Houston, TX, USA

    Punit Kaur

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O’Sullivan Coyne, G., Monge, C., Chen, A.P. (2019). Role of HSP90 Inhibitors in the Treatment of Cancer. In: Asea, A., Kaur, P. (eds) Heat Shock Protein 90 in Human Diseases and Disorders. Heat Shock Proteins, vol 19. Springer, Cham. https://doi.org/10.1007/978-3-030-23158-3_6

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