Integrins as A New Target for Cancer Treatment

Abstract

Despite the great progress in the development of targeted therapies for different types of cancer utilizing monoclonal antibodies (e.g., cetuximab for colorectal cancer and head and neck cancer therapy), kinase inhibitors (e.g., sorafenib for kidney cancer and gastrointestinal stromal tumours therapy), and immunomodulatory treatments (e.g., nivolumab and pembrolizumab for melanoma therapy and lung cancer therapy), there is still a need to search for new, more effective treatments. Integrins are responsible for intercellular adhesion and interaction with the cellular matrix. The function of integrins is related to the transduction of intracellular signals associated with adhesion, migration, cell proliferation, differentiation, and apoptosis. Molecules targeting integrins that lead to cancer cell death have been developed. The most advanced molecules studied in clinical trials are abituzumab, intetumumab and cilengitide. There are different groups of anti-integrin drugs: monoclonal antibodies (e.g., abituzumab) and other such as cilengitide, E7820 and MK-0429. These drugs have been evaluated in various cancer types. However, they have shown modest efficacy, and none of them have yet been approved for cancer treatment. Studies have shown that patient selection using biomarkers might improve the efficacy of anti-integrin cancer treatment. Many preclinical models have demonstrated promising results using integrin visualization for cancer detection and treatment efficacy monitoring; however, these strategies require further evaluation in humans.

Keywords: Integrins; cancer treatment; monoclonal antibodies; signal transduction; targeted therapy; transmembrane glycoproteins..