Title:Crosstalk between IGF-1R and other Tumor Promoting Pathways
Volume: 20
Issue: 17
Author(s): Changyu Liu, Zheng Zhang, Hexiao Tang, Zhixiao Jiang, Liangkun You and Yongde Liao
Affiliation:
Keywords:
Insulin-like growth factor 1 receptor, receptor tyrosine kinases, steroids, tumorigenesis, cancer, crosstalk, cell signaling, cotargeting.
Abstract: Insulin-like growth factor 1 receptor (IGF-1R) is important in cancer pathogenesis and progression. While its signaling pathway
is an interesting therapeutic target, recent clinical trials have exhibited limited effects; however, significant crosstalks between IGF-
1R and other signaling pathways have garnered increasing attention. These complex networks include interactions between IGF-1R and
receptor tyrosine kinases (RTKs), including insulin receptor (IR), epidermal growth factor receptor (EGFR), vascular endothelial growth
factor receptor (VEGFR), mesenchymal-epithelial transition factor (MET), platelet-derived growth factor receptor (PDGFR), and fibroblast
growth factor receptor (FGFR). Furthermore, IGF-1R also is related to steroid hormones, including estrogen receptors alpha and
beta (ER! and ER"), androgen receptor (AR), and progesterone receptor (PR). Cumulatively, actions of crosstalk between IGF-1R, and
RTKs/steroid hormones promote tumorigenesis, as demonstrated by the effectiveness of recently proposed therapeutic strategies. These
therapeutic strategies, primarily pertaining to crosstalk-cotargeting, exhibited notable advantages in overcoming resistance to conventional
chemotherapy and conventional endocrine therapy. Furthermore, these techniques offer benefits beyond the limited effects of single-
agent targeting previously reported. Thus, the role of crosstalk between IGF-1R and RTKs/steroid hormones, including strategies to
block these pathways in combination with recent development in this field, were reviewed and the potential future cancer therapeutics
suggested by this rationale were considered.
