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Therapeutic Strategies to Block the Hypoxic Response

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Hypoxia and Cancer Metastasis

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1136))

Abstract

Patients with the low levels of O2 (hypoxia) in their primary tumors have a higher risk for metastasis and death, indicating a need to therapeutically inhibit the effectors of hypoxia. Many strategies have been developed and investigated to block the hypoxic response. For example, inhibitors of HIF-1 and HIF-2 function by altering the transcription, translation, dimerization, nuclear translocation, DNA-binding, or ubiquitination of the HIF proteins. Hypoxia-activated prodrugs inhibit the hypoxic response through hypoxia-mediated reduction of an inactive, or minimally active, chemical to a cytotoxic agent. Most hypoxia-activated prodrugs function by inducing DNA damage, but others with more novel functions, including prodrugs that release EGFR/HER2 inhibitors also exist. Despite the existence of many therapeutics to combat the hypoxic response, there has been very little success in late phase clinical trials, potentially due to a lack of biomarkers that can be used to stratify patients who would benefit from a hypoxia-targeted therapy.

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Authors and Affiliations

  1. Breast and Ovarian Cancer Program, Department of Oncology, The Johns Hopkins School of Medicine, Baltimore, MD, USA

    Josh W. DiGiacomo & Daniele M. Gilkes

  2. Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA

    Josh W. DiGiacomo & Daniele M. Gilkes

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  1. Josh W. DiGiacomo
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  2. Daniele M. Gilkes
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Correspondence to Daniele M. Gilkes .

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  1. Breast and Ovarian Cancer Program, Department of Oncology, The Johns Hopkins School of Medicine, Baltimore, MD, USA

    Daniele M. Gilkes

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DiGiacomo, J.W., Gilkes, D.M. (2019). Therapeutic Strategies to Block the Hypoxic Response. In: Gilkes, D. (eds) Hypoxia and Cancer Metastasis. Advances in Experimental Medicine and Biology, vol 1136. Springer, Cham. https://doi.org/10.1007/978-3-030-12734-3_10

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