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Updated: Dec 3, 2025
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Automated Preparation of [68Ga]Ga-3BP-3940 on a Synthesis Module for PET Imaging of the Tumor Microenvironment
Published on: April 25, 2025
Cell surface GRP78: An emerging imaging marker and therapeutic target for cancer
Masoud Farshbaf1, Ahmad Yari Khosroushahi1, Solmaz Mojarad-Jabali2
1Department of Medical Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran; Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Abstract:
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.
Insights
Targeting cell surface glucose-regulated protein 78 (csGRP78) offers a novel strategy to eradicate heterogeneous cancer cells, including resistant subpopulations. This approach holds promise for improved cancer therapy and imaging, addressing limitations of current treatments.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Cancer's heterogeneity and resistance to therapeutics necessitate novel targeting strategies.
- Existing treatments often fail to eliminate all cancer cells, leading to recurrence and mortality.
- Cell surface glucose-regulated protein 78 (csGRP78), overexpressed in cancer, presents a potential therapeutic and imaging target.
Purpose of the Study:
- To review the biological roles, functional significance, and translocation mechanisms of csGRP78 in tumor cells.
- To explore the potential of csGRP78 as a biomarker for targeted cancer therapy and imaging.
- To outline future directions for csGRP78-targeted theranostics.
Main Methods:
- Literature review of studies on GRP78 biology and cancer cell surface expression.
- Analysis of GRP78's role in endoplasmic reticulum stress and cancer progression.
- Examination of GRP78 translocation mechanisms to the cell surface.
Main Results:
- GRP78, a heat shock protein 70 family member, functions as a molecular chaperone.
- Cell surface GRP78 (csGRP78) is significantly overexpressed on various cancer cells and angiogenic endothelial cells.
- csGRP78's presence facilitates targeted delivery of therapeutic and imaging agents.
Conclusions:
- csGRP78 is a promising biomarker for developing targeted cancer therapies and diagnostic imaging agents.
- Targeting csGRP78 can potentially overcome limitations of current cancer treatments by eradicating heterogeneous and drug-resistant cells.
- Further research into csGRP78 targeting is crucial for advancing theranostic applications in oncology.
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