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Molecular Pathways

Molecular Pathways: Hypoxia-Activated Prodrugs in Cancer Therapy

Natalia Baran and Marina Konopleva
Natalia Baran
Section of Molecular Hematology and Therapy, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
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Marina Konopleva
Section of Molecular Hematology and Therapy, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
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  • For correspondence: mkonople@mdanderson.org
DOI: 10.1158/1078-0432.CCR-16-0895 Published May 2017
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Abstract

Hypoxia is a known feature of aggressive solid tumors as well as a critical hallmark of the niche in aggressive hematologic malignances. Hypoxia is associated with insufficient response to standard therapy, resulting in disease progression and curtailed patients' survival through maintenance of noncycling cancer stem–like cells. A better understanding of the mechanisms and signaling pathways induced by hypoxia is essential to overcoming these effects. Recent findings demonstrate that bone marrow in the setting of hematologic malignancies is highly hypoxic, and that progression of the disease is associated with expansion of hypoxic niches and stabilization of the oncogenic hypoxia-inducible factor-1alpha (HIF1α). Solid tumors have also been shown to harbor hypoxic areas, maintaining survival of cancer cells via the HIF1α pathway. Developing new strategies for targeting hypoxia has become a crucial approach in modern cancer therapy. The number of preclinical and clinical trials targeting low-oxygen tumor compartments or the hypoxic bone marrow niche via hypoxia-activated prodrugs is increasing. This review discusses the development of the hypoxia-activated prodrugs and their applicability in treating both hematologic malignancies and solid tumors. Clin Cancer Res; 23(10); 2382–90. ©2017 AACR.

  • Received October 12, 2016.
  • Revision received December 16, 2016.
  • Accepted December 19, 2016.
  • ©2017 American Association for Cancer Research.
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Clinical Cancer Research: 23 (10)
May 2017
Volume 23, Issue 10
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Molecular Pathways: Hypoxia-Activated Prodrugs in Cancer Therapy
Natalia Baran and Marina Konopleva
Clin Cancer Res May 15 2017 (23) (10) 2382-2390; DOI: 10.1158/1078-0432.CCR-16-0895

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Molecular Pathways: Hypoxia-Activated Prodrugs in Cancer Therapy
Natalia Baran and Marina Konopleva
Clin Cancer Res May 15 2017 (23) (10) 2382-2390; DOI: 10.1158/1078-0432.CCR-16-0895
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Clinical Cancer Research
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