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Therapeutic Implications of Heat Shock Proteins in Cancer

  • Maxim ShevtsovEmail author
  • Gabriele Multhoff
Chapter
Part of the Heat Shock Proteins book series (HESP, volume 16)

Abstract

Evolutionary conserved members of the main heat shock protein families (HSP) are highly overexpressed in many tumor cells where they contribute to protein homeostasis, cytoprotection, cell survival, tumor progression and therapy resistance. Upon cell proliferation and differentiation but also in response to a large variety of different stressors, including anticancer radio- and/or chemotherapy, the synthesis of stress-inducible HSP is further upregulated. Therefore, the inhibition of members of the HSP90, HSP70 and small heat shock proteins (i.e., HSP20, clusterin) in cancer cells has emerged as a promising approach in translational and clinical oncology to break therapy resistance. Moreover, HSP have been found to play key roles in eliciting anti-tumor immune responses by acting as carriers for tumor-specific immunogenic peptides, chaperokines, adjuvants for antigen presentation, or targets for the innate immune system. HSP-based immunotherapies have shown promising results in the therapy of certain subtypes of tumors.

Keywords

Adaptive immunity Cancer vaccine Clusterin Geldanamycin Heat shock proteins HSP20 HSP70 HSP90-families Immunotherapy Radicicol 

Abbreviations

15-DSG

15-deoxyspergualin

17-AAG

17-(allylamino)-17-demethoxygeldanamycin

17-DMAG

17-desmethoxy-17-N,N-dimethylaminoethylaminogeldanamycin

ADP

Adenosine diphosphate

Aha1

Activator of Hsp90 ATPase

APCs

Antigen presenting cells

ATP

Adenosine triphosphate

Az

Apoptozole

Cdc37

Cell cycle division protein 37

Clever-1

Common lymphatic endothelial and vascular endothelial receptor-1

CLL

Chronic lymphocytic leukemia

CML

Chronic myelogenous leukemia

EGCG

Epigallocatechin gallate

EGF

Epidermal growth factor

EGFR

Epidermal growth factor receptor

FEEL-1

Fascilin EGF-like scavenger receptor-1

GDA

Geldanamycin

GIST

Gastrointestinal stromal tumors

HCC

Hepatocellular carcinoma

HDAC

Histone deacetylase family

HER2

Human epidermal growth factor receptor 2

HoP

HSP70/HSP90 organizing protein

HSF-1

Heat shock factor 1

HSP

Heat shock protein (family)

IFN-γ

Interferon gamma

IL

Interleukin

IPI-504

17-allylamino-17-demethoxygeldanamycin hydroquinone hydrochloride

LOX-1

Low-density lipoprotein receptor-1

MHC

Major histocompatibility complex

MKT-077

1-ethyl-2-[[3-ethyl-5-(3-methylbenzothiazolin 2-yliden)]-4-oxothiazolidin-2-ylidenemethyl] pyridinium chloride

mTOR

Mechanistic target of rapamycin

NEF

Nucleotide exchange factor

NF-κB

Nuclear factor kappa-light-chain-enhancer of activated B cells

NK cells

Natural killer cells

NO

Nitric oxide

PD

Platycodin D

PES

Phenylethynesulfonamide (pifithrin-μ)

RDC

Radicicol

ROS

Reactive oxygen species

sCLU

Small clusterin

SREC-1

Scavenger receptor expressed by endothelial cells-1

Stab-1

Stabilin-1

TLR

Toll-like receptor

Notes

Acknowledgements

The study was supported by the Alexander von Humboldt Stiftung, by a grant from Russian Foundation for Basic Research 15-08-08148A, in part by a grant of the Russian Science Foundation 14-50-00068 and by the Federal Agency of Scientific Organizations, Russia and by a grant of the Deutsche Forschungsgemeinschaft (DFG SFB824/3, STA 1520/1-1, MAP), BMBF (01GU0823, 02NUK038A) and BMWi (AiF project), Germany. This work was supported by the german Research Foundation (DFG) and the Technische Universität München within the funding programme Open Access Publishing. The authors are grateful to Nan-Jong Lee for preparation of the Figures.

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Center for Translational Cancer Research (TranslaTUM), Radiation Immuno Oncology GroupTechnische Universität München (TUM)MunichGermany
  2. 2.Institute of Cytology of the Russian Academy of Sciences (RAS)St. PetersburgRussia
  3. 3.Pavlov First Saint Petersburg State Medical UniversitySt. PetersburgRussia
  4. 4.Polenov Russian Scientific Research Institute of NeurosurgerySt. PetersburgRussia

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