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Drug Target Encyclopedia Series (21) —SDC1
Release Time：
2025-12-05 14:33
SDC1 (Syndecan-1, also known as CD138) is a transmembrane heparan sulfate proteoglycan that regulates cell adhesion, proliferation, and signaling in epithelial and plasma cells.
Overexpression of SDC1 is a hallmark of multiple myeloma and several solid tumors, contributing to tumor progression, metastasis, and therapy resistance.
SDC1 is overexpressed in:
• Multiple myeloma (plasma cell malignancy marker)
• Breast cancer
• Pancreatic and colorectal cancers
• Lung and liver cancers (subsets)
Targeting SDC1 in oncology:
- Monoclonal antibodies (mAbs) – Designed to block SDC1-mediated signaling and tumor–microenvironment interactions.
- Antibody-drug conjugates (ADCs) – Target SDC1+ cancer cells with cytotoxic payloads for selective killing; e.g., indatuximab ravtansine (BT062) has shown promise in multiple myeloma.
- CAR-T and CAR-NK cell therapies – SDC1-directed CAR-Ts are under clinical investigation, showing activity against relapsed/refractory multiple myeloma.
- Bispecific antibodies – Redirect immune cells to eliminate SDC1-expressing tumor cells.
- RNA-based approaches – Emerging RNAi and mRNA platforms are being explored to regulate SDC1 expression in tumor models.
Challenges include:
• Tumor heterogeneity and dynamic expression of SDC1 on plasma cells
• Potential off-tumor effects on normal epithelial cells
• Managing immunosuppression within the bone marrow microenvironment
🔬 Ongoing research is focused on next-generation SDC1-targeted ADCs, dual-target CAR constructs (e.g., BCMA/SDC1), and combination strategies with immunomodulatory drugs (IMiDs) or checkpoint inhibitors to enhance antitumor efficacy.
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