Heat shock protein 90 inhibition: rationale and clinical potential

被引：46

作者：

Den, Robert B. ^{[2
]}

Lu, Bo ^{[1
]}

机构：

[1] Thomas Jefferson Univ, Jefferson Med Coll, Dept Radiat Oncol, Bodine Canc Ctr, Philadelphia, PA 19107 USA

[2] Thomas Jefferson Univ, Jefferson Med Coll, Dept Radiat Oncol, Philadelphia, PA 19107 USA

来源：

THERAPEUTIC ADVANCES IN MEDICAL ONCOLOGY | 2012年 / 4卷 / 04期

关键词：

clinical trial; heat shock protein 90; pharmacological inhibition;

D O I：

10.1177/1758834012445574

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Heat shock protein 90 (HSP90) is a molecular chaperone protein essential for cellular survival. Functionally, HSPs promote proper protein folding, prevent misfolding, and restore three-dimensional protein structure which is critical following toxic cellular stresses. Recently, targeting HSP90 pharmacologically has gained traction in cancer therapy. Oncogenic cells depend on their ability to withstand endogenous (anoxia, nutrient deprivation, pH changes, and deranged signaling pathways) and exogenous (chemotherapy and radiation therapy) stressors for survival. Pharmacological inhibition of HSP90 destabilizes proteins and leads to degradation through the proteasome. This article will review the utility of HSP90 inhibition, as well as the current adoption in clinical trials and practice.

引用

页码：211 / 218

页数：8

共 55 条

[1] Phase I pharmacokinetic and pharmacodynarnic study of 17-allylamino, 17-demethoxygeldanamycin in patients with advanced malignancies [J].

Banerji, U ;

O'Donnell, A ;

Scurr, M ;

Pacey, S ;

Stapleton, S ;

Asad, Y ;

Simmons, L ;

Maloney, A ;

Raynaud, F ;

Campbell, M ;

Walton, M ;

Lakhani, S ;

Kaye, S ;

Workman, P ;

Judson, I .

JOURNAL OF CLINICAL ONCOLOGY, 2005, 23 (18) :4152-4161

[2] CUDC-305, a Novel Synthetic HSP90 Inhibitor with Unique Pharmacologic Properties for Cancer Therapy [J].

Bao, Rudi ;

Lai, Cheng-Jung ;

Qu, Hui ;

Wang, Dagong ;

Yin, Ling ;

Zifcak, Brian ;

Atoyan, Ruzanna ;

Wang, Jing ;

Samson, Maria ;

Forrester, Jeffrey ;

DellaRocca, Steven ;

Xu, Guang-Xin ;

Tao, Xu ;

Zhai, Hai-Xiao ;

Cai, Xiong ;

Qian, Changgeng .

CLINICAL CANCER RESEARCH, 2009, 15 (12) :4046-4057

[3] Divergent synthesis of a pochonin library targeting HSP90 and in vivo efficacy of an identified inhibitor [J].

Barluenga, Sofia ;

Wang, Cuihua ;

Fontaine, Jean-Gonzague ;

Aouadi, Kaiss ;

Beebe, Kristin ;

Tsutsumi, Shinji ;

Neckers, Len ;

Winssinger, Nicolas .

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2008, 47 (23) :4432-4435

[4] Re: Role of the heat shock response and molecular chaperones in oncogenesis and cell death [J].

Blagosklonny, MV .

JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2001, 93 (03) :239-240

[5]

Bonvini P, 2002, CANCER RES, V62, P1559

[6] Combining Hit Identification Strategies: Fragment-Based and in Silico Approaches to Orally Active 2-Aminothieno[2,3-d]pyrimidine Inhibitors of the Hsp90 Molecular Chaperone [J].

Brough, Paul A. ;

Barril, Xavier ;

Borgognoni, Jenifer ;

Chene, Patrick ;

Davies, Nicholas G. M. ;

Davis, Ben ;

Drysdale, Martin J. ;

Dymock, Brian ;

Eccles, Suzanne A. ;

Garcia-Echeverria, Carlos ;

Fromont, Christophe ;

Hayes, Angela ;

Hubbard, Roderick E. ;

Jordan, Allan M. ;

Jensen, Michael Rugaard ;

Massey, Andrew ;

Merrett, Angela ;

Padfield, Antony ;

Parsons, Rachel ;

Radimerski, Thomas ;

Raynaud, Florence I. ;

Robertson, Alan ;

Roughley, Stephen D. ;

Schoepfer, Joseph ;

Simmonite, Heather ;

Sharp, Swee Y. ;

Surgenor, Allan ;

Valenti, Melanie ;

Walls, Steven ;

Webb, Paul ;

Wood, Mike ;

Workman, Paul ;

Wright, Lisa .

JOURNAL OF MEDICINAL CHEMISTRY, 2009, 52 (15) :4794-4809

[7] SNX2112, a synthetic heat shock protein 90 inhibitor, has potent antitumor activity against HER kinase-dependent cancers [J].

Chandarlapaty, Sarat ;

Sawai, Ayana ;

Ye, Qing ;

Scott, Anisa ;

Silinski, Melanie ;

Huang, Ken ;

Fadden, Pat ;

Partdrige, Jeff ;

Hall, Steven ;

Steed, Paul ;

Norton, Larry ;

Rosen, Neal ;

Solit, David B. .

CLINICAL CANCER RESEARCH, 2008, 14 (01) :240-248

[8] ANALYSIS OF HEAT-SHOCK PROTEIN EXPRESSION IN MYELOID-LEUKEMIA CELLS BY FLOW-CYTOMETRY [J].

CHANT, ID ;

ROSE, PE ;

MORRIS, AG .

BRITISH JOURNAL OF HAEMATOLOGY, 1995, 90 (01) :163-168

[9] HEAT-SHOCK PROTEIN-HSP70 IN PATIENTS WITH AXILLARY LYMPH NODE-NEGATIVE BREAST-CANCER - PROGNOSTIC IMPLICATIONS [J].

CIOCCA, DR ;

CLARK, GM ;

TANDON, AK ;

FUQUA, SAW ;

WELCH, WJ ;

MCGUIRE, WL .

JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1993, 85 (07) :570-574

[10] Reaction of geldanamycin and C17-substituted analogues with glutathione: Product identifications and pharmacological implications [J].

Cysyk, RL ;

Parker, RJ ;

Barchi, JJ ;

Steeg, PS ;

Hartman, NR ;

Strong, JA .

CHEMICAL RESEARCH IN TOXICOLOGY, 2006, 19 (03) :376-381

← 1 2 3 4 5 6 →