Relationship between hypoxia and response to antiangiogenic therapy in metastatic colorectal cancer

Paola Ulivi _, Giorgia Marisi and Alessandro Passardi

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Oncotarget. 2016; 7:46678-46691. https://doi.org/10.18632/oncotarget.8712

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Paola Ulivi1, Giorgia Marisi1 and Alessandro Passardi2

1 Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy

2 Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy

Correspondence to:

Alessandro Passardi, email:

Keywords: metastatic colorectal cancer, hypoxia, angiogenesis, bevacizumab, antiangiogenic therapy

Received: January 25, 2016 Accepted: March 31, 2016 Published: April 12, 2016


Colorectal cancer remains a major public health problem worldwide. Despite the introduction of antiangiogenic drugs for the treatment of metastatic disease, a large number of issues remains unresolved. In particular, studies on predictive biomarkers of response and pathways of resistance to these agents are lacking, making it difficult to accurately select candidates for treatment. Hypoxia is the prime driving force for tumor angiogenesis and a vicious cycle between hypoxia and angiogenesis can be observed in tumors. Anti-angiogenic drugs act inhibiting tumor vasculature and, as consequence, inducing hypoxia. However, hypoxia could, in turn, induce an increase of metastatic potential of cells and a series of phenomena that could induce drug resistance. In the present review biological mechanisms of hypoxia and its relation with angiogenesis, and resistance to antiangiogenic therapy will be discussed. Moreover, data from clinical trials on antiangiogenic drugs in metastatic colorectal cancer will be reviewed, and the role of hypoxia in monitoring the response to treatment will be analysed. Combination strategies using anti-angiogenic and hypoxia inhibiting drugs are also discussed as they constitute promising field of research.

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