Relation of the IGF/IGF1R system to autophagy in colitis and colorectal cancer

• Published in: World journal of gastroenterology : WJG 2017-12, Vol.23 (46), p.8109-8119
• Main Authors: Sipos, Ferenc, Székely, Hajnal, Kis, Imre Dániel, Tulassay, Zsolt, Műzes, Györgyi
• Format: Article
• Language: English
• Subjects: Review
• ISSN: 1007-9327; 2219-2840
• DOI: 10.3748/wjg.v23.i46.8109

Metabolic syndrome(Met S), as a chronic inflammatory disorder has a potential role in the development of inflammatory and cancerous complications of the colonic tissue. The interaction of DNA damage and inflammation is affected by the insulin-like growth factor 1 receptor(IGF1 R) signaling pathway. The IGF1 R pathway has been reported to regulate autophagy, as well, but sometimes through a bidirectional context. Targeting the IGF1 R-autophagy crosstalk could represent a promising strategy for the development of new antiinflammatory and anticancer therapies, and may help for subjects suffering from Met S who are at increased risk of colorectal cancer. However, therapeutic responses to targeted therapies are often shortlived, since a signaling crosstalk of IGF1 R with other receptor tyrosine kinases or autophagy exists, leading to acquired cellular resistance to therapy. From a pharmacological point of view, it is attractive to speculate that synergistic benefits could be achieved by inhibition of one of the key effectors of the IGF1 R pathway, in parallel with the pharmacological stimulation of the autophagy machinery, but cautiousness is also required, because pharmacologic IGF1 R modulation can initiate additional, sometimes unfavorable biologic effects.