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Are Integrins Still Practicable Targets for Anti-Cancer Therapy?

1
Pathology Unit, Department of Oncology, Microbiology and Immunology, Faculty of Science and Medicine, University of Fribourg, Chemin du Musée 18, Per 17, CH-1700 Fribourg, Switzerland
2
Departments of Neurological Surgery, Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center, Neurology and Medicine, Feinberg School of Medicine, Northwestern University, 676 N St Clair St, Suite 2210, Chicago, IL 60611, USA
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(7), 978; https://doi.org/10.3390/cancers11070978
Received: 1 June 2019 / Revised: 27 June 2019 / Accepted: 9 July 2019 / Published: 12 July 2019
(This article belongs to the Special Issue The Role of Integrins in Cancer)
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Abstract

Correlative clinical evidence and experimental observations indicate that integrin adhesion receptors, in particular those of the αV family, are relevant to cancer cell features, including proliferation, survival, migration, invasion, and metastasis. In addition, integrins promote events in the tumor microenvironment that are critical for tumor progression and metastasis, including tumor angiogenesis, matrix remodeling, and the recruitment of immune and inflammatory cells. In spite of compelling preclinical results demonstrating that the inhibition of integrin αVβ3/αVβ5 and α5β1 has therapeutic potential, clinical trials with integrin inhibitors targeting those integrins have repeatedly failed to demonstrate therapeutic benefits in cancer patients. Here, we review emerging integrin functions and their proposed contribution to tumor progression, discuss preclinical evidence of therapeutic significance, revisit clinical trial results, and consider alternative approaches for their therapeutic targeting in oncology, including targeting integrins in the other cells of the tumor microenvironment, e.g., cancer-associated fibroblasts and immune/inflammatory cells. We conclude that integrins remain a valid target for cancer therapy; however, agents with better pharmacological properties, alternative models for their preclinical evaluation, and innovative combination strategies for clinical testing (e.g., together with immuno-oncology agents) are needed. View Full-Text
Keywords: cancer; angiogenesis; tumor microenvironment; imaging; therapy cancer; angiogenesis; tumor microenvironment; imaging; therapy
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Alday-Parejo, B.; Stupp, R.; Rüegg, C. Are Integrins Still Practicable Targets for Anti-Cancer Therapy? Cancers 2019, 11, 978.

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