Targeting hypoxic response for cancer therapy

Elisa Paolicchi _, Federica Gemignani, Marija Krstic-Demonacos, Shoukat Dedhar, Luciano Mutti and Stefano Landi

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Oncotarget. 2016; 7:13464-13478. https://doi.org/10.18632/oncotarget.7229

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Elisa Paolicchi1, Federica Gemignani1, Marija Krstic-Demonacos2, Shoukat Dedhar3, Luciano Mutti2,* and Stefano Landi1,*

1 Genetics-Department of Biology, University of Pisa, Pisa, Italy

2 School of Environment and Life Sciences, College of Science and Technology, University of Salford, Salford, UK

3 Department of Integrative Oncology, BC Cancer Research Centre, BC Cancer Agency and Department of Biochemistry and Molecular Biology, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada

* Senior authors

Correspondence to:

Elisa Paolicchi, email:

Keywords: hypoxia, Warburg effect, cancer stem cells, epithelial mesenchymal transition, clinical trials

Received: August 04, 2015 Accepted: January 17, 2016 Published: February 07, 2016


Hypoxic tumor microenvironment (HTM) is considered to promote metabolic changes, oncogene activation and epithelial mesenchymal transition, and resistance to chemo- and radio-therapy, all of which are hallmarks of aggressive tumor behavior. Cancer cells within the HTM acquire phenotypic properties that allow them to overcome the lack of energy and nutrients supply within this niche. These phenotypic properties include activation of genes regulating glycolysis, glucose transport, acidosis regulators, angiogenesis, all of which are orchestrated through the activation of the transcription factor, HIF1A, which is an independent marker of poor prognosis. Moreover, during the adaptation to a HTM cancer cells undergo deep changes in mitochondrial functions such as “Warburg effect” and the “reverse Warburg effect”.

This review aims to provide an overview of the characteristics of the HTM, with particular focus on novel therapeutic strategies currently in clinical trials, targeting the adaptive response to hypoxia of cancer cells.

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