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Updated: Jul 1, 2025
Gene Regulation and Targeted Therapy in Gastric Cancer Peritoneal Metastasis: Radiological Findings from Dual Energy CT and PET/CT
Published on: January 22, 2018
Targeting cell surface glucose-regulated protein 94 in gastric cancer with an anti-GRP94 human monoclonal antibody
Hyun Jung Kim1, Yea Bin Cho2, Kyun Heo3
1Department of Biopharmaceutical Chemistry, Kookmin University, Seoul 02707, Korea.
Abstract:
Gastric cancer (GC), a leading cause of cancer-related mortality, remains a significant challenge despite recent therapeutic advancements. In this study, we explore the potential of targeting cell surface glucose-regulated protein 94 (GRP94) with antibodies as a novel therapeutic approach for GC. Our comprehensive analysis of GRP94 expression across various cancer types, with a specific focus on GC, revealed a substantial overexpression of GRP94, highlighting its potential as a promising target. Through in vitro and in vivo efficacy assessments, as well as toxicological analyses, we found that K101.1, a fully human monoclonal antibody designed to specifically target cell surface GRP94, effectively inhibits GC growth and angiogenesis without causing in vivo toxicity. Furthermore, our findings indicate that K101.1 promotes the internalization and concurrent downregulation of cell surface GRP94 on GC cells. In conclusion, our study suggests that cell surface GRP94 may be a potential therapeutic target in GC, and that antibody-based targeting of cell surface GRP94 may be an effective strategy for inhibiting GRP94-mediated GC growth and angiogenesis. [BMB Reports 2024; 57(4): 188-193].
Insights
Targeting cell surface glucose-regulated protein 94 (GRP94) with the K101.1 antibody shows promise for gastric cancer (GC) therapy. This antibody effectively inhibits GC growth and angiogenesis without toxicity, offering a new therapeutic avenue.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Gastric cancer (GC) remains a major cause of cancer mortality, necessitating novel therapeutic strategies.
- Glucose-regulated protein 94 (GRP94) is significantly overexpressed in GC, presenting a potential therapeutic target.
- Current advancements in GC treatment highlight the need for innovative approaches.
Discussion:
- Antibody-based targeting of cell surface GRP94 offers a novel therapeutic strategy for GC.
- The fully human monoclonal antibody K101.1 specifically targets cell surface GRP94.
- K101.1 demonstrates efficacy in inhibiting GC growth and angiogenesis in vitro and in vivo.
Key Insights:
- GRP94 is substantially overexpressed across various cancer types, particularly in gastric cancer.
- The K101.1 antibody effectively inhibits GC growth and angiogenesis without inducing in vivo toxicity.
- K101.1 promotes the internalization and downregulation of cell surface GRP94 on GC cells.
Outlook:
- Cell surface GRP94 represents a promising therapeutic target for gastric cancer.
- Antibody-mediated targeting of GRP94 may provide an effective strategy against GC growth and angiogenesis.
- Further research into GRP94-targeted therapies could lead to improved outcomes for gastric cancer patients.
