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HSP90 and Its Inhibitors for Cancer Therapy: Use of Nano-delivery System to Improve Its Clinical Application

  • Prathap Somu
  • Subhankar PaulEmail author
Chapter
Part of the Heat Shock Proteins book series (HESP, volume 19)

Abstract

The molecular chaperone HSP90 (heat shock protein 90) has become a crucial target in cancer therapeutics as its function has been implicated with various types of malignant transformation. Numerous HSP90 inhibitors have been identified so far and many of them have also been clinically tested. Although most of these are natural or their derived inhibitors including geldanamycin and its derivatives 17-AAG and 17-DMAG have shown efficacy, their easy success has been hindered in various stages of the clinical studies due to poor solubility and cytotoxicity. However, recently substantial published documents reported that the systemic targeting of the HSP90 inhibitors using nano-based drug delivery system could provide a possible clinical solution to overcome their limitation. In this chapter, we review the initial development of various HSP90 inhibitors from natural to synthetically derived one and their clinical studies. We also review their limitations and future perspectives as a possible potential agent in the cancer therapeutics by their systemic and control delivery to the target site using the nano-drug delivery system. Also, the application of combined therapy has also been discussed in the current chapter using HSP90 inhibitors and nanocarrier. In addition, we also discuss the therapeutic approaches like photothermal where nano carrier is not only used as a carrier for the systemic delivery of HSP90 inhibitors but also as a therapeutic agent.

Keywords

Cancer Heat shock proteins Molecular chaperone Nanomaterials Targeted delivery Therapeutic index 

Abbreviations

17-AAG

17-allylamino-17demethoxygeldanamycin

17-DMAG

17-(2-dimethylaminoethyl)amino-17-demethoxygeldanamycin

ADP

adenosine diphosphate

AhR

aryl hydrocarbon receptor

ATP

adenosine triphosphate

CBR

clinical benefit rate

DLT

dose-limiting toxicities

EGCG

Epigallocatechin 3-gallate

FDG-PET

fluorodeoxyglucose positron emission tomography

GIST

gastrointestinal stromal tumors

GM

Geldanamycin

HOP

HSP90 organizing protein

HSP

heat shock protein

IPI-493

17-desmethoxy-17-amino Geldanamycin

IPI-504

17-allylamino-17-demethoxygeldanamycin Hydroquinone Hydro-chloride

MDR

multi-drug resistance

MTD

maximum tolerated dose

NSCLC

non-small-cell lung carcinoma

ORR

overall response rate

PBMC

peripheral blood mononuclear cells

PCL

poly(ε-caprolactone)

PDGFRA

platelet-derived growth factor receptor alpha

PEG

poly(ethylene glycol)

PET

positron emission tomography

PLGA

poly (lactic-co-glycolic acid)

PR

partial response

RD

radicicol

SD

stable diseases

SUV

standardized uptake value

TNBC

triple-negative breast cancer

Notes

Acknowledgements

The authors sincerely thank the Science and Engineering Research Board, Government of India, for financial support (Grant No. SERB/F/4290/2016-17) and National Institute of Technology Rourkela, Government of India, for providing the infrastructural facility for the preparation of the chapter.

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Authors and Affiliations

  1. 1.Structural Biology & Nanomedicine Laboratory, Department of Biotechnology & Medical EngineeringNational Institute of Technology RourkelaRourkelaIndia

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