Cell surface GRP78: An emerging imaging marker and therapeutic target for cancer

JOURNAL OF CONTROLLED RELEASE

卷:328

Review

Farshbaf, Masoud^1,2  Khosroushahi, Ahmad Yari^1,2  Mojarad-Jabali, Solmaz³  Zarebkohan, Amir¹  Valizadeh, Hadi⁴  Walker, Paul R.^5,6 

[1] Tabriz Univ Med Sci, Fac Adv Med Sci, Dept Med Nanotechnol, Tabriz, Iran

[2] Tabriz Univ Med Sci, Drug Appl Res Ctr, Tabriz, Iran

[3] Tabriz Univ Med Sci, Fac Pharm, Dept Pharmaceut Nanotechnol, Tabriz, Iran

[4] Tabriz Univ Med Sci, Fac Pharm, Dept Pharmaceut, Tabriz 51664, Iran

[5] Geneva Univ Hosp, Ctr Translat Res Onco Hematol, Div Oncol, Geneva, Switzerland

[6] Univ Geneva, Geneva, Switzerland

关键词: GRP78;    Cancer;    Nanomedicine;    Active targeting;    Therapy;    Imaging;   

DOI  :  10.1016/j.jconrel.2020.10.055

来源: Elsevier

【 摘 要 】

As one of the deadliest diseases, cancer frequently resists existing therapeutics because they do not target all cells within a progressing tumor, for example both tumor stem and proliferating cells. This frequently results in enrichment of invasive and metastatic drug-resistant tumor cells subpopulations, cancer recurrence and eventually, patient mortality. Thus, there is an urgent need to identify specific markers, by which the targeted imaging and/or therapeutic guided missile-like agents can specifically detect and/or eradicate all cancer cells within a heterogeneous tumor, while leaving the normal cells intact. As a member of heat shock protein 70 (HSP70) superfamily, glucose regulated protein 78 (GRP78) has been documented as a molecular chaperone in the endoplasmic reticulum (ER) which mainly responds to ER stresses in normal cells. There is over-expression of GRP78 on the surface of cancer cells and angiogenic endothelial cells, which makes it a promising target for different types of peptides and antibodies that can be employed for targeted cancer therapy or imaging. In this review, we discuss the biological processes, functional importance and translocation mechanisms of cell surface GRP78 (csGRP78) in tumor cells. As a cancer biomarker, we also review the potential applications of csGRP78 targeted therapy and imaging and finally we suggest a brief roadmap ahead of csGRP78 targeting for targeted theranostic implications.

【 授权许可】

Free