Key result
Targeting the IGF system shows therapeutic potential in sarcomas via novel regulators.
Why the study?
The IGF system is involved in sarcoma cell regulation but clinical trials targeting it have been largely disappointing, with exceptions in Ewing sarcoma.
This review highlights the potential of targeting the IGF system in sarcomas and identifies novel regulators like IGF2BPs, DDRs, and PAPP-A for future therapeutic exploitation.
IGF-1R inhibition remains investigational in sarcomas; leaves open biomarker-guided trials in Ewing sarcoma.
The insulin-like growth factor (IGF) system has gained substantial interest due to its involvement in regulating cell proliferation, differentiation and survival during anoikis and after conventional and targeted therapies. However, results from clinical trials have been largely disappointing, with only a few but notable exceptions, such as trials targeting sarcomas, especially Ewing sarcoma. This review highlights key studies focusing on IGF signaling in sarcomas, specifically studies underscoring the properties that make this system an attractive therapeutic target and identifies new relationships that may be exploited. This review discusses the potential roles of IGF2 mRNA-binding proteins (IGF2BPs), discoidin domain receptors (DDRs) and metalloproteinase pregnancy-associated plasma protein-A (PAPP-A) in regulating the IGF system. Deeper investigation of these novel regulators of the IGF system may help us to further elucidate the spatial and temporal control of the IGF axis, as understanding the control of this axis is essential for future clinical studies.
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Mancarella et al. (2017) conducted a review in Sarcomas, especially Ewing sarcoma. IGF system targeting was evaluated. The insulin-like growth factor (IGF) system is an attractive therapeutic target in sarcomas, with novel regulators like IGF2BPs, DDRs, and PAPP-A offering potential for future clinical exploitation.
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