Emerging Cancer Therapeutic Targets in Protein Homeostasis

被引：27

作者：

Bastola, Prabhakar ^{[1
,2
]}

Oien, Derek B. ^{[1
]}

Cooley, Megan ^{[3
]}

Chien, Jeremy ^{[1
]}

机构：

[1] Univ New Mexico, Hlth Sci Ctr, Dept Internal Med, Div Mol Med, 915 Camino de Salud NE, Albuquerque, NM 87131 USA

[2] Univ Kansas, Med Ctr, Dept Pharmacol Toxicol & Therapeut, Kansas City, KS 66130 USA

[3] PRA Hlth Sci, Small Mol, Methods Dev, Lenexa, KS 66215 USA

来源：

AAPS JOURNAL | 2018年 / 20卷 / 06期

关键词：

autophagy; heat shock proteins; protein quality control; ubiquitin proteasome system; unfolded protein response; ENDOPLASMIC-RETICULUM STRESS; PROTEASOME INHIBITOR BORTEZOMIB; PHASE-I TRIAL; HEAT-SHOCK RESPONSE; ER STRESS; AAA-ATPASE; SOLID TUMORS; SELECTIVE-INHIBITION; AGGRESOME FORMATION; QUALITY-CONTROL;

D O I：

10.1208/s12248-018-0254-1

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Genomic aberrations inside malignant cells through copy number alterations, aneuploidy, and mutations can exacerbate misfolded and unfolded protein burden resulting in increased proteotoxic stress. Increased proteotoxic stress can be deleterious to malignant cells; therefore, these cells rely heavily on the protein quality control mechanisms for survival and proliferation. Components of the protein quality control, such as the unfolded protein response, heat shock proteins, autophagy, and the ubiquitin proteasome system, orchestrate a cascade of downstream events that allow the mitigation of the proteotoxic stress. This dependency makes components of the protein quality control mechanisms attractive targets in cancer therapeutics. In this review, we explore the components of the protein homeostasis especially focusing on the emerging cancer therapeutic agents/targets that are being actively pursued actively.

引用

页数：15

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