VEGFC
Overview
VEGFC (Vascular Endothelial Growth Factor C) is a secreted growth factor that promotes angiogenesis and lymphangiogenesis by binding VEGFR-2 and VEGFR-3. In melanoma, VEGFC is transcriptionally up-regulated in pre-treatment tumors that do not respond to anti-PD-1 immunotherapy, co-enriched as part of the innate anti-PD-1 resistance (IPRES) transcriptional signature.
Alterations observed in the corpus
- Transcriptionally up-regulated in non-responding pretreatment melanoma tumors treated with anti-PD-1; co-enriched within the IPRES (innate anti-PD-1 resistance) transcriptional signature alongside VEGFA, IL10, and mesenchymal-transition transcripts PMID:26997480.
Cancer types (linked)
- SKCM: VEGFC up-regulation is part of the immunosuppressive/angiogenic gene expression program (IPRES) associated with innate resistance to anti-PD-1 therapy in melanoma (n=28 RNA-seq pretreatment samples) PMID:26997480.
Co-occurrence and mutual exclusivity
Therapeutic relevance
- VEGFC up-regulation as part of IPRES suggests that anti-angiogenic combination strategies (targeting VEGF signaling) could potentially overcome innate anti-PD-1 resistance in melanoma; not directly tested in the citing study PMID:26997480.
Open questions
- Whether pharmacological suppression of VEGFC (or VEGF signaling broadly) can restore anti-PD-1 sensitivity in IPRES-high tumors is unresolved; the IPRES signature is correlative, not causally validated.
Sources
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