Molecular pathways: Hypoxia-activated prodrugs in cancer therapy

Natalia Baran, Marina Konopleva

Research output: Contribution to journalReview articlepeer-review

96 Scopus citations

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 news trategies 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.

Original languageEnglish (US)
Pages (from-to)2382-2390
Number of pages9
JournalClinical Cancer Research
Volume23
Issue number10
DOIs
StatePublished - May 15 2017

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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