IGF2/IGF1R Signaling as a Therapeutic Target in MYB-Positive Adenoid Cystic Carcinomas and Other Fusion Gene-Driven Tumors

Cells. 2019 Aug 16;8(8):913. doi: 10.3390/cells8080913.


Chromosome rearrangements resulting in pathogenetically important gene fusions are a common feature of many cancers. They are often potent oncogenic drivers and have key functions in central cellular processes and pathways and encode transcription factors, transcriptional co-regulators, growth factor receptors, tyrosine kinases, and chromatin modifiers. In addition to being useful diagnostic biomarkers, they are also targets for development of new molecularly targeted therapies. Studies in recent decades have shown that several oncogenic gene fusions interact with the insulin-like growth factor (IGF) signaling pathway. For example, the MYB-NFIB fusion in adenoid cystic carcinoma is regulated by IGF1R through an autocrine loop, and IGF1R is a downstream target of the EWSR1-WT1 and PAX3-FKHR fusions in desmoplastic small round cell tumors and alveolar rhabdomyosarcoma, respectively. Here, we will discuss the mechanisms behind the interactions between oncogenic gene fusions and the IGF signaling pathway. We will also discuss the role of therapeutic inhibition of IGF1R in fusion gene driven malignancies.

Keywords: FET oncogenes; IGF signaling; IGF1R; IGF2; MYB; adenoid cystic carcinoma; carcinoma; gene fusions; salivary gland tumor; sarcoma.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Biomarkers / metabolism
  • Carcinoma, Adenoid Cystic* / genetics
  • Carcinoma, Adenoid Cystic* / metabolism
  • Humans
  • Insulin-Like Growth Factor II / metabolism*
  • NFI Transcription Factors / metabolism
  • Oncogene Fusion*
  • Oncogene Proteins, Fusion / metabolism*
  • Proto-Oncogene Proteins c-myb / metabolism
  • Receptor, IGF Type 1 / metabolism*
  • Salivary Gland Neoplasms* / genetics
  • Salivary Gland Neoplasms* / metabolism


  • Biomarkers
  • IGF1R protein, human
  • IGF2 protein, human
  • MYB protein, human
  • NFI Transcription Factors
  • NFIB protein, human
  • Oncogene Proteins, Fusion
  • Proto-Oncogene Proteins c-myb
  • Insulin-Like Growth Factor II
  • Receptor, IGF Type 1