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Updated: Dec 11, 2025

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GRP78 targeting: Hitting two birds with a stone.

Abdo A Elfiky1, Ahmed M Baghdady1, Shehab A Ali1

  • 1Biophysics Department, Faculty of Sciences, Cairo University, Giza, Egypt.

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|August 26, 2020
PubMed
Summary

Glucose regulating protein 78 (GRP78) is a key protein in the endoplasmic reticulum stress response. Targeting cell-surface GRP78 shows promise for cancer therapy, viral infections, and diagnostic imaging.

Keywords:
BiPCancer-targetingGRP78Natural compoundsPeptide inhibitorsSARS-CoV-2

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Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Glucose regulating protein 78 (GRP78), also known as Heat Shock Protein Family A Member 5 (HSPA5), is a crucial chaperone protein.
  • GRP78 regulates the Unfolded Protein Response (UPR) within the endoplasmic reticulum (ER) lumen.

Purpose of the Study:

  • To review the therapeutic and diagnostic applications of targeting GRP78.
  • To explore GRP78's role in cancer, viral, and fungal infections.

Main Methods:

  • Summarizing existing research on GRP78 overexpression in various cell types.
  • Analyzing studies utilizing GRP78 as a therapeutic target for cancer and infections.
  • Reviewing GRP78's application in diagnostic and imaging modalities.

Main Results:

  • GRP78 overexpression is observed on the cell membrane of cancer cells and cells infected with viruses or fungi.
  • Cell-surface GRP78 serves as a target for cancer therapy using peptides, antibodies, and natural compounds.
  • GRP78 targeting is effective against viral infections, including SARS-CoV-2, and fungal infections.

Conclusions:

  • Cell-surface GRP78 is a validated target for cancer therapy and reducing viral infectivity.
  • GRP78-based strategies are employed in diagnostic and imaging applications using radionuclides.
  • Targeting GRP78 offers a versatile approach for both therapeutic interventions and diagnostic purposes.