IGF1R

Overview

IGF1R (insulin-like growth factor 1 receptor) encodes a receptor tyrosine kinase that mediates the mitogenic and anti-apoptotic effects of IGF1 and IGF2. In cancer pharmacogenomics, IGF1R expression is a lineage-enriched predictor of sensitivity to IGF-1R inhibitors in multiple myeloma, supporting the development of targeted therapies in this disease.

Alterations observed in the corpus

  • High IGF1R expression in multiple myeloma cell lines correlates with AEW541 (IGF-1R inhibitor) sensitivity in the CCLE pharmacogenomic profiling of 947 cancer cell lines PMID:22460905
  • Rare amplification event (<1% of patients) identified through the CNA-expression landscape in METABRIC (2,000 tumors); potentially relevant for tyrosine kinase inhibitor targeting PMID:22522925
  • Mutated in breast cancer (TCGA, 510 tumors); somatic alterations identified across intrinsic subtypes PMID:23000897
  • Located within a cluster-2 focal amplification at 15q26.2 in endometrial carcinoma; identified as a potential therapeutic target in the TCGA endometrial corpus analysis PMID:23636398
  • IGF1R focally amplified in 2.7% of rhabdomyosarcoma (RMS) cases; identified as part of the 93%-targetable kinase signaling axis with approved or late-stage inhibitors PMID:24436047
  • Activated in ~21% of HCC; part of the IGF axis (alongside IGF2 overexpression and IGF2R allelic loss) implicated as a therapeutic target in HCC PMID:24735922
  • IGF1R is listed as a candidate RTK alteration in HNSC (n=279 TCGA) with somatic events across HPV(+) and HPV(−) groups in the multi-platform genomic analysis. PMID:25631445
  • Novel amplification target gene in lung SqCC identified in the TCGA pan-lung cancer cohort PMID:27158780
  • IGF1R amplified in subsets of esophageal adenocarcinoma (EAC) alongside ERBB2, EGFR, VEGFA, and KRAS amplifications PMID:28052061.
  • Part of the PI3K/AKT/MTOR pathway co-alteration cluster (with PTEN, AKT3, MTOR, RICTOR) in 84% of ULMS+STLMS iCluster C1 vs 44% of STLMS C2 (p=1e-04); upregulated in poor-prognosis STLMS C1 in TCGA SARC (n=80 LMS). PMID:29100075

Cancer types (linked)

  • MM (multiple myeloma): High IGF1R expression is enriched in multiple myeloma lines and predicts AEW541 sensitivity; multiple myeloma is highlighted as a promising indication for IGF-1R inhibitor clinical trials PMID:22460905

Co-occurrence and mutual exclusivity

  • IGF1R and IGF1 are co-expressed at high levels in multiple myeloma cell lines and both function as predictive features for AEW541 sensitivity PMID:22460905

Therapeutic relevance

  • High IGF1R expression predicts sensitivity to AEW541 (IGF-1R inhibitor) across 947 cancer cell lines in the CCLE; multiple myeloma is specifically proposed as a priority indication for IGF-1R-targeted therapy based on lineage-enriched co-expression of IGF1 and IGF1R PMID:22460905

Open questions

  • Clinical validation of IGF1R expression as a predictive biomarker for IGF-1R inhibitor response in multiple myeloma patients is needed to translate CCLE pharmacogenomic findings.

Sources

This page was processed by crosslinker on 2026-05-14. - PMID:22522925

This page was processed by crosslinker on 2026-05-14. - PMID:23000897

This page was processed by crosslinker on 2026-05-14. - PMID:23636398

This page was processed by crosslinker on 2026-05-14. - PMID:24436047

This page was processed by crosslinker on 2026-05-14. - PMID:24735922

This page was processed by crosslinker on 2026-05-14. - PMID:25631445

This page was processed by crosslinker on 2026-05-14. - PMID:27158780

This page was processed by entity-page-writer on 2026-05-15. - PMID:28052061

This page was processed by entity-page-writer on 2026-05-15. - PMID:29100075

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