Key Points
• Source: Acta Pharmaceutica Sinica B
• Conclusion/Relevance: “Here, we discuss the evidence and knowledge on the contribution of integrins to cancer biology. Furthermore, we summarize the clinical attempts targeting this family in anti-cancer therapy development.”
• Integrins are transmembrane receptors that play a role in various physiological and pathological processes. They mediate cell–extracellular matrix and cell–cell interactions, and contribute to fibrosis, inflammation, thrombosis, and tumor metastasis. In terms of tumor progression, they are promising targets for cancer treatment. Integrin antagonists, such as antibodies and synthetic peptides, have been effectively used for cancer therapy.
• “Integrins signaling in cancer involves not only activation of certain pathways downstream of specific receptors, but also crosstalk with growth factors, growth factor receptors, cytokines, oncogenes, and enzymes,” wrote the authors. One example of integrin crosstalk is VEGF/VEGFR interaction on endothelial cells—not tumor cells—thus promoting tumor angiogenesis.
• Recent research has highlighted the strong antitumor effects of integrin targeted therapy, such as mAbs and synthetic molecules. Clinical assays, however, have not demonstrated this effect on tumor-progression inhibition.
• The authors wrote that disappointing results with regard to “patient survival time, disease stabilization, and occurrence of metastasis may be due to the complexity of integrin mechanisms, the development of resistance to anoikis, and their ability to compensate each other and induce a poor phenotype. Using a more complex mechanism, a vessel co-option was reported as a pathway that allows tumor cells to receive nutrients from blood via pre-existing vasculature without developing new vessels as a resistance response against anti-angiogenic therapy …. In addition, studies have also shown that improper doses of integrin inhibitors may break the balance and produce the opposite effect.”
• Integrin inhibition may be a target for drug development in cancer therapy when added to other targeted therapies, such as tyrosine kinase inhibitors, anti-growth factors antibodies, or CAR-T therapy. Further preclinical studies, however, are needed to determine all the potential escape methods by tumor cells.