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Review
. 2020 Jun 3;13(1):64.
doi: 10.1186/s13045-020-00904-3.

Insulin-like growth factor receptor signaling in tumorigenesis and drug resistance: a challenge for cancer therapy

Hui Hua  1 , Qingbin Kong  2 , Jie Yin  2 , Jin Zhang  2 , Yangfu Jiang  3
Affiliations
Review

Insulin-like growth factor receptor signaling in tumorigenesis and drug resistance: a challenge for cancer therapy

Hui Hua et al. J Hematol Oncol. .

Abstract

Insulin-like growth factors (IGFs) play important roles in mammalian growth, development, aging, and diseases. Aberrant IGFs signaling may lead to malignant transformation and tumor progression, thus providing the rationale for targeting IGF axis in cancer. However, clinical trials of the type I IGF receptor (IGF-IR)-targeted agents have been largely disappointing. Accumulating evidence demonstrates that the IGF axis not only promotes tumorigenesis, but also confers resistance to standard treatments. Furthermore, there are diverse pathways leading to the resistance to IGF-IR-targeted therapy. Recent studies characterizing the complex IGFs signaling in cancer have raised hope to refine the strategies for targeting the IGF axis. This review highlights the biological activities of IGF-IR signaling in cancer and the contribution of IGF-IR to cytotoxic, endocrine, and molecular targeted therapies resistance. Moreover, we update the diverse mechanisms underlying resistance to IGF-IR-targeted agents and discuss the strategies for future development of the IGF axis-targeted agents.

Keywords: Cancer; Drug resistance; Insulin-like growth factor; Receptor tyrosine kinase; Tumorigenesis.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
IGF, insulin, and their receptors. IGF can be secreted by the liver, cancer cells, and macrophages, while insulin is secreted by pancreatic β cells. IGF-IR may heterodimerize with InsR-A or InsR-B and then forms a hybrid receptor. Whereas IGFBPs usually act as serum reservoirs for IGFs, IGFBP7, in particular, may compete with IGFs to bind to IGF-IR and inhibit the activation of IGF-IR. GH, growth hormone
Fig. 2
Fig. 2
IGF and insulin signaling pathways. IGF and insulin can activate multiple signaling pathways including PI3K, MAPK, JAK/STAT, discoidin domain receptors (DDRs), FAK, and Src; promote cell proliferation, survival, epithelial-mesenchymal transition (EMT), migration, and stemness; and inhibit autophagy and anoikis
Fig. 3
Fig. 3
The mechanisms for resistance to anti-IGF-IR agents. RTKs, receptor tyrosine kinases
See this image and copyright information in PMC

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