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Updated: May 5, 2026
In vivo Bioluminescence Imaging of Tumor Hypoxia Dynamics of Breast Cancer Brain Metastasis in a Mouse Model
Published on: October 3, 2011
Hypoxia-directed drug strategies to target the tumor microenvironment
Michael P Hay1, Kevin O Hicks, Jingli Wang
1Auckland Cancer Society Research Centre, The University of Auckland, 92019, Auckland, 1142, New Zealand, m.hay@auckland.ac.nz.
Abstract:
Hypoxia is an important component of the tumor microenvironment and has been the target of drug discovery efforts for almost half a century. These efforts have evolved from offsetting the impact of hypoxia on radiotherapy with oxygen-mimetic radiosensitizers to using hypoxia as a means to selectively target tumors. The more recent description of hypoxia-inducible factors and their role in the hypoxia response network has revealed a host of new drug targets to selectively target tumors. We are developing hypoxia-directed drugs in each of the following areas: novel radiosensitizers for hypofractionated radiotherapy, a second-generation benzotriazine di-N-oxide hypoxia-activated prodrug, and a hypoxia-inducible factor-1-dependent cytotoxin that targets glucose transport. These projects are discussed in the context of hypoxia-directed drug discovery.
Insights
Hypoxia, a hallmark of the tumor microenvironment, is being targeted by novel drugs. These hypoxia-directed therapies include radiosensitizers and cytotoxins for improved cancer treatment.
Area of Science:
- Oncology
- Pharmacology
- Biochemistry
Background:
- Hypoxia is a critical component of the tumor microenvironment.
- Targeting tumor hypoxia has been a focus of drug discovery for decades.
- Hypoxia-inducible factors (HIFs) offer new therapeutic targets.
Purpose of the Study:
- To develop novel hypoxia-directed drugs for cancer therapy.
- To explore new strategies for targeting tumors using hypoxia.
- To discuss current projects in hypoxia-directed drug discovery.
Main Methods:
- Development of novel radiosensitizers for hypofractionated radiotherapy.
- Creation of a second-generation hypoxia-activated prodrug (benzotriazine di-N-oxide).
- Design of a hypoxia-inducible factor-1 dependent cytotoxin targeting glucose transport.
Main Results:
- Multiple hypoxia-directed drug candidates are under development.
- These candidates target different aspects of the hypoxia response network.
- The research focuses on selective tumor targeting via hypoxia.
Conclusions:
- Hypoxia-directed drug discovery offers promising avenues for cancer treatment.
- Targeting HIFs and related pathways can lead to effective therapies.
- Advancements in understanding tumor hypoxia are driving new drug development.
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