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Heat Shock Proteins in Signaling Pathways pp 397–429Cite as

HSP90 Inhibitors Blocking Multiple Oncogenic Signaling Pathways for the Treatment of Cancer

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Part of the book series: Heat Shock Proteins ((HESP,volume 17))

Abstract

Heat shock protein 90 (HSP90) is an ATP-dependent molecular chaperone which plays important roles in the development of cancer. Inhibition of the HSP90 chaperone function can disrupt multiple cancer dependent signaling pathways and result in potent anti-cancer effects, which has been a promising anti-cancer strategy. Up to now, HSP90 inhibitors with different mechanisms have been developed, including HSP90 N-terminal inhibitors (pan-isoform and isoform selective), C-terminal inhibitors and HSP90-cochaperone protein-protein interaction (PPI) inhibitors. In this chapter, we will review the current development of HSP90 inhibitors as anti-cancer agents.

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Abbreviations

BTZ:

bortezomib

CR:

complete response

CTD:

C-terminal domain

DHPM:

3,4-dihydropyrimidin-2-(1H)-one

DLTs:

dose-limiting toxicities

EGCG:

epigallocatechin gallate

ER:

endoplasmic reticulum

ESCC:

esophageal squamous cell carcinoma

FU:

5-fluorouracil

GRP94:

glucose-regulated protein 94

HGF:

hepatocyte growth factor

HSP:

Heat shock protein

HTRF:

homogeneous time-resolved fluorescence

IGFs:

insulin-like growth factors

IRI:

irinotecan

l-OHP:

oxaliplatin

MD:

middle-domain

MM:

multiple myeloma

MTD:

maximum tolerance dose

NSCLC:

non-small cell lung cancer

NTD:

N-terminal domain

PPI:

protein-protein interaction

PR:

partial response

RDA:

radamide

SD:

stable disease

SDH:

succinate dehydrogenase

SPR:

surface plasmon resonance

TEAEs:

treatment-related adverse events

TRAIL:

TNF-α–related apoptosis-inducing ligand

TRAMP:

transgenic adenocarcinoma of the mouse prostate

TRAP1:

tumor necrosis factor receptor-associated protein-1

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Acknowledgements

This work is supported by Projects 81872737 and 81773639 of the National Natural Science Foundation of China; 2632018ZD15 of the Key Program of China Pharmaceutical University; 2017ZX0-9302003, and 2018ZX09711002-003-006 of the National Major Science and Technology Project of China (Innovation and Development of New Drugs).

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  1. State Key Laboratory of Natural Medicines and Jiang Su Key Laboratory of Drug Design and Optimization and Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing, China

    Fen Jiang, Xiao-Li Xu & Qi-Dong You

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  1. Fen Jiang
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  2. Xiao-Li Xu
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  3. Qi-Dong You
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Correspondence to Qi-Dong You .

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  1. Professor, 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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Jiang, F., Xu, XL., You, QD. (2019). HSP90 Inhibitors Blocking Multiple Oncogenic Signaling Pathways for the Treatment of Cancer. In: Asea, A., Kaur, P. (eds) Heat Shock Proteins in Signaling Pathways. Heat Shock Proteins, vol 17. Springer, Cham. https://doi.org/10.1007/978-3-030-03952-3_20

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