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Drug Target Encyclopedia Series (16) —PDGFRA
Release Time：
2025-12-05 14:05
PDGFRA (platelet-derived growth factor receptor alpha) is a receptor tyrosine kinase that regulates cell proliferation, survival, and differentiation. Aberrant PDGFRA activation—through gene mutations, amplifications, or overexpression—drives oncogenic signaling across multiple tumor types, making it an important therapeutic target.
PDGFRA is implicated in:
• Gastrointestinal stromal tumors (GIST), especially the D842V mutation subtype
• Glioblastoma and other gliomas
• Acute myeloid leukemia (AML)
• Lung cancer and other solid tumors
Targeting PDGFRA in therapy:
- Tyrosine kinase inhibitors (TKIs) – Imatinib revolutionized GIST treatment, while newer agents like Avapritinib and Crenolanib target resistant PDGFRA mutations.
- Monoclonal antibodies & ADCs – Investigational agents aim to selectively block PDGFRA-driven signaling.
- RNA-based and CAR-T approaches – Emerging modalities explore novel ways to modulate or eliminate PDGFRA+ tumor cells.
Challenges include:
• Resistance mutations (e.g., PDGFRA D842V and secondary kinase domain alterations)
• Tumor heterogeneity across PDGFRA-driven cancers
• Need for reliable biomarkers to guide patient selection
🔬 Ongoing research is focused on next-generation TKIs, rational drug combinations, and immunotherapeutic strategies to overcome resistance and broaden therapeutic benefit.
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