Insulin/IGF-driven cancer cell-stroma crosstalk as a novel therapeutic target in pancreatic cancer

Molecular Cancer
Ayse Ceren MutganIhsan Ekin Demir

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is unrivalled the deadliest gastrointestinal cancer in the western world. There is substantial evidence implying that insulin and insulin-like growth factor (IGF) signaling axis prompt PDAC into an advanced stage by enhancing tumor growth, metastasis and by driving therapy resistance. Numerous efforts have been made to block Insulin/IGF signaling pathway in cancer therapy. However, therapies that target the IGF1 receptor (IGF-1R) and IGF subtypes (IGF-1 and IGF-2) have been repeatedly unsuccessful. This failure may not only be due to the complexity and homology that is shared by Insulin and IGF receptors, but also due to the complex stroma-cancer interactions in the pancreas. Shedding light on the interactions between the endocrine/exocrine pancreas and the stroma in PDAC is likely to steer us toward the development of novel treatments. In this review, we highlight the stroma-derived IGF signaling and IGF-binding proteins as potential novel therapeutic targets in PDAC.

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Methods Mentioned

BETA
nucleotide exchange
pancreatectomy

Clinical Trials Mentioned

NCT00630552
NCT01231347
NCT00819169
NCT00617708
NCT00769483
NCT01971034
NCT02978547
NCT02399137
NCT02431676
NCT01385956

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