2. Academic Validation
  3. Poliovirus Receptor as a Potential Target in Gastric Signet-Ring Cell Carcinoma for Antibody-Drug Conjugate Development

Poliovirus Receptor as a Potential Target in Gastric Signet-Ring Cell Carcinoma for Antibody-Drug Conjugate Development

  • Cancers (Basel). 2026 Jan 15;18(2):270. doi: 10.3390/cancers18020270.
Yinxia Zhao 1 2 3 4 5,  Hanfei Xie 5 6,  Xuefei Tian 5 7 8,  Li Yuan 2 3 4,  Can Hu 2 3 4,  Yujie Dai 5 9,  Shengjie Zhang 2 3 4,  Peng Guo 1 2 3 4 5,  Xiangdong Cheng 1 2 3 4 5
Affiliations

Affiliations

  • 1 Faculty of Medicine, School of Life Sciences, Tianjin University, Tianjin 300072, China.
  • 2 Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou 310022, China.
  • 3 Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital, Hangzhou 310022, China.
  • 4 Zhejiang Key Lab of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer, Zhejiang Cancer Hospital, Hangzhou 310022, China.
  • 5 Clinical and Translational Research Center, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou 310018, China.
  • 6 Department of Gynecologic Oncology, Zhejiang Cancer Hospital, Postgraduate Training Base Alliance of Wenzhou Medical University, Hangzhou 310022, China.
  • 7 School of Molecular Medicine, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences (UCAS), Hangzhou 310022, China.
  • 8 Department of Biological Medicines and Shanghai Engineering Research Center of Immunotherapeutics, Fudan University, Shanghai 201203, China.
  • 9 MOE Frontier Science Centre for Precision Oncology, Faculty of Health Sciences, University of Macau, Macau SAR 999078, China.
PMID: 41595191 DOI: 10.3390/cancers18020270
Abstract

Background: Gastric signet-ring cell carcinoma (GSRCC) is a distinct subtype of gastric Cancer characterized by unique biological features, leading to low rates of early diagnosis, poor prognosis, and limited response to chemotherapy and immunotherapy. Effective targeted therapies for GSRCC remain scarce. Given these treatment challenges and the potential efficacy of antibody-drug conjugates (ADCs) in clinical settings, this study focuses on identifying novel ADCs with significant potential to improve the treatment outcomes of GSRCC.

Methods: We conducted a comprehensive bioinformatics analysis of GSRCC using multi-omics data (including transcriptomics and proteomics) and identified the poliovirus receptor (PVR) as a potential therapeutic target for GSRCC. We selected deruxtecan (DXd) as an effective carrier for developing an ADC targeting GSRCC. The synthesized PVR monoclonal antibody-DXd complex (PVR-DXd) has a drug-to-antibody ratio (DAR) of 4.

Results: PVR-DXd demonstrated potent antitumor activity in a human GSRCC xenograft model, effectively eliminating tumors while sparing normal tissue, highlighting its potential as a novel and impactful targeted therapy for this aggressive subtype of gastric signet ring cell carcinoma.

Conclusions: This preliminary study supports the further development of PVR-DXd as a candidate therapy for advanced GSRCC.

Keywords

ADC; GSRCC; PVR; proteomics analysis; targeted therapy.

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