KDR

Overview

KDR (also known as VEGFR2) encodes vascular endothelial growth factor receptor 2, a key mediator of VEGF/VEGFR signaling in angiogenesis. In angiosarcoma, KDR alterations include amplification and gain-of-function point mutations. Notably, KDR is more frequently altered in sporadic angiosarcoma than in radiation-associated angiosarcoma.

Alterations observed in the corpus

  • Amplification and gain-of-function (GOF) point mutations in 11% of RT-ANGS vs 24% of sporadic AS; depleted in RT-AS relative to sporadic AS PMID:37350195.
  • Significantly mutated in LUAD (TSP, n=188); 4 kinase domain mutations; rare amplifications suggesting proto-oncogene role; mutations suggest potential benefit from VEGFR inhibitors such as sorafenib or sunitinib. PMID:18948947
  • KDR (VEGFR2) is an anti-angiogenic target in NPC; inhibited by apatinib (VEGFR2 TKI, + camrelizumab ORR 43.3% in ICI-refractory R/M NPC), surufatinib, axitinib, anlotinib, and cabozantinib. PMID:24952746
  • KDR (VEGFR2) identified as a low-frequency FDA-druggable alteration in HCC (<1% frequency); co-amplified with KIT and PDGFRA at 4q12 in the Triple-WT melanoma subtype PMID:25822088
  • KDR co-amplified with KIT and PDGFRA at 4q12 in Triple-WT cutaneous melanoma (TCGA 333-sample cohort); part of rationale for sorafenib, crenolanib, regorafenib, and pazopanib in this subtype PMID:26091043
  • KDR (VEGFR2) mutations observed at low frequency in ATC as part of RTK alterations alongside FLT1 and FLT4; reported among hits with ≥2 ATC occurrences in a 341-gene panel sequencing study PMID:26878173
  • Amplification at PDGFRA/KIT/KDR locus is among the candidate Ras/Raf/RTK pathway events that raise the fraction of lung ADCs with an actionable driver to 76%; enriched in oncogene-negative lung ADC PMID:27158780
  • KDR amplification observed in 4 ACYC patients co-amplified with PDGFRA and KIT in a cohort of 151 advanced head and neck tumors; these patients were treated with regorafenib PMID:27442865
  • KDR amplification (4 patients) was among additional alterations contributing to the actionable-alteration list in 180 advanced germ cell tumors profiled by MSK-IMPACT PMID:27646943
  • KDR (VEGFR2) overexpression identified in pediatric osteosarcoma (OS) as a multi-targeted kinase inhibitor (MTKI) target; patient received matched treatment PMID:28007021.

Cancer types (linked)

  • ANGS — KDR alterations (amplification, GOF point mutations) are depleted in RT-AS (11%) compared to sporadic AS (24%); part of the VEGF/VEGFR signaling pathway PMID:37350195.

Co-occurrence and mutual exclusivity

  • No specific co-occurrence or mutual exclusivity relationships with KDR reported in the corpus.

Therapeutic relevance

  • KDR is part of the VEGF/VEGFR signaling pathway identified as activated in RT-AS alongside FLT4 and HRAS, representing a potential therapeutic target PMID:37350195.

Open questions

  • Whether the lower frequency of KDR alterations in RT-AS vs sporadic AS reflects a distinct biology or reduced dependence on VEGFR2 signaling in the radiation-associated setting is unknown PMID:37350195.

Sources

This page was processed by crosslinker on 2026-05-14. - PMID:18948947

This page was processed by crosslinker on 2026-05-14. - PMID:24952746

This page was processed by crosslinker on 2026-05-14. - PMID:25822088

This page was processed by crosslinker on 2026-05-14. - PMID:26091043

This page was processed by crosslinker on 2026-05-14. - PMID:26878173

This page was processed by entity-page-writer on 2026-05-15. - PMID:27158780

This page was processed by entity-page-writer on 2026-05-15. - PMID:27442865

This page was processed by entity-page-writer on 2026-05-15. - PMID:27646943

This page was processed by entity-page-writer on 2026-05-15. - PMID:28007021

This page was processed by entity-page-writer on 2026-05-15.