Related Experiment Video
Updated: Mar 22, 2026
In Vivo Model for Testing Effect of Hypoxia on Tumor Metastasis
Published on: December 9, 2016
Relationship between hypoxia and response to antiangiogenic therapy in metastatic colorectal cancer
Paola Ulivi1, Giorgia Marisi1, Alessandro Passardi2
1Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
Abstract:
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.
Insights
Hypoxia drives colorectal cancer growth and resistance to anti-angiogenic drugs. Understanding this link is key to improving treatment selection and developing new therapies.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Colorectal cancer (CRC) is a significant global health challenge.
- Anti-angiogenic drugs offer treatment for metastatic CRC, but patient selection and resistance mechanisms remain problematic.
- Tumor hypoxia and angiogenesis are interconnected, with anti-angiogenic therapy potentially exacerbating hypoxia and promoting resistance.
Purpose of the Study:
- To review the biological mechanisms of hypoxia and its relationship with angiogenesis.
- To discuss the role of hypoxia in resistance to anti-angiogenic therapy in metastatic colorectal cancer.
- To analyze clinical trial data and explore combination strategies involving anti-angiogenic and hypoxia-inhibiting drugs.
Main Methods:
- Literature review of biological mechanisms of hypoxia and angiogenesis.
- Analysis of clinical trial data for anti-angiogenic drugs in metastatic colorectal cancer.
- Discussion of emerging combination strategies.
Main Results:
- Hypoxia is a critical factor in tumor angiogenesis and a driver of resistance to anti-angiogenic therapies.
- Anti-angiogenic drugs can induce or worsen hypoxia, potentially increasing tumor cell metastasis and drug resistance.
- Clinical data highlights the need for better biomarkers to predict response and manage resistance.
Conclusions:
- Hypoxia plays a dual role in anti-angiogenic therapy for colorectal cancer, promoting resistance.
- Targeting hypoxia in combination with anti-angiogenic agents presents a promising therapeutic strategy.
- Further research into hypoxia-related biomarkers is essential for optimizing treatment selection and outcomes.
Related Concept Videos
01:24Regulation of Angiogenesis and Blood Supply
02:49Cancer Therapies
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
02:53Adaptive Mechanisms in Cancer Cells
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
01:23Hypoxia
Types of Hypoxia
There are four primary types of hypoxia, each resulting from a different cause:
1. Anemic hypoxia: This type occurs due to insufficient oxygen delivery caused by a lack of red blood cells (RBCs) or RBCs with abnormal or...