Exploiting the cancer niche: Tumor-associated macrophages and hypoxia as promising synergistic targets for nano-based therapy

Silva, Vera and Al-Jamal, Wafa' T. (2017) Exploiting the cancer niche: Tumor-associated macrophages and hypoxia as promising synergistic targets for nano-based therapy. Journal of Controlled Release, 253. 82–96. ISSN 0168-3659

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Abstract

The tumor microenvironment has been widely exploited as an active participant in tumor progression. Extensive reports have defined the dual role of tumor-associated macrophages (TAMs) in tumor development. The protumoral effect exerted by the M2 phenotype has been correlated with a negative outcome in most solid tumors. The high infiltration of immune cells in the hypoxic cores of advanced solid tumors leads to a chain reaction of stimuli that enhances the expression of protumoral genes, thrives tumor malignancy, and leads to the emergence of drug resistance. Many studies have shown therapeutic targeting systems, solely to TAMs or tumor hypoxia, however, novel therapeutics that target both features are still warranted. In the present review, we discuss the role of hypoxia in tumor development and the clinical outcome of hypoxia-targeted therapeutics, such as hypoxia-inducible factor (HIF-1) inhibitors and hypoxia-activated prodrugs. Furthermore, we review the state-of-the-art of macrophage-based cancer therapy. We thoroughly discuss the development of novel therapeutics that simultaneously target TAMs and tumor hypoxia. Nano-based systems have been highlighted as interesting strategies for dual modality treatments, with somewhat improved tissue extravasation. Such approach could be seen as a promising strategy to overcome drug resistance and enhance the efficacy of chemotherapy in advanced solid and metastatic tumors, especially when exploiting cell-based nanotherapies. Finally, we provide an in-depth opinion on the importance of exploiting the tumor microenvironment in cancer therapy, and how this could be translated to clinical practice.

Item Type: Article
Uncontrolled Keywords: cancer hypoxia,tumor-associated macrophages,tumor microenvironment,targeted cancer therapy,nanomedicine
Faculty \ School: Faculty of Science > School of Pharmacy
Faculty of Science
Related URLs:
Depositing User: Pure Connector
Date Deposited: 14 Mar 2017 01:41
Last Modified: 22 Apr 2020 02:57
URI: https://ueaeprints.uea.ac.uk/id/eprint/62952
DOI: 10.1016/j.jconrel.2017.03.013

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