Cancer Research

Hallmarks of Cancer 2: Angiogenesis

Figure from Hanahan, Douglas, and Robert A. Weinberg. “The hallmarks of cancer.” cell 100.1 (2000): 57-70.

Angiogenesis

Angiogenesis is another hallmark that cancer cells must achieve – a growing tumour will induce the formation of new blood vessels to provide nutrients and oxygen.

Like normal cells, cancers cells require blood vessels in order to survive. The cells need to be near enough to a blood vessel for oxygen to diffuse to them and toxic carbon dioxide to be removed. One of the hallmarks of cancer is the ability to encourage new blood vessels to form to sustain a growing tumour, this is called angiogenesis.

Like a weed killed at its roots

Without the formation of blood vessels around a growing tumour the cells will starve of oxygen and die. Due to this reliance of tumours on angiogenesis it is a target for cancer therapy – if we can stop tumours from creating new blood vessels they will not be able to grow.

A new compound

Research carried out at the University of Kentucy, USA, showed that quercertin, a naturally derived compound found in fruits and vegetables, could prevent angiogenesis when administered at safe levels.

Pratheeshkumar and colleagues demonstrated that this drug could prevent the growth and invasion of endothelial cells, the precursor cell from which blood vessels are made. Quercertin prevented blood vessels forming by interfering with vascular endothelial growth factor, or VEGF, signalling*. VEGF is one of the most important signalling proteins in angiogenesis and quercertin was shown to act on the VEGF receptor preventing this signalling. By targetting VEGF signalling, quercertin caused cell death, slowed tumour growth and tube formation, and stopped angiogenesis.

VEGF signalling is the target of the currently approved anti-angiogenic treatment, bevacizumab. This drug is used to treat bowel, lung, and breast cancer. Bevacizumab is an antibody that binds to VEGF preventing it from binding to its receptor – treatment with bevacizumab slows angiogensis and therefore tumour growth. Research such as that by Pratheeshkumar and others are identifying new ways to inhibit VEGF and other pro-angiogenic pathways in the hope to produce more efficient cancer drugs.

For more reading try the angiogenesis review paper by Grothey and Allegra, which talks about the use of anti-angiogenic agents in the treatment of metastatic colorectal cancer (mCRC). As well as summarising angiogenic targets for the development of drugs, the paper reviews future anti-angiogenic VEGF drugs that are currently in phase II and III clinical trial.

References:

Pratheeshkumar, Poyil, et al. “Quercetin Inhibits Angiogenesis Mediated Human Prostate Tumor Growth by Targeting VEGFR-2 Regulated AKT/mTOR/P70S6K Signaling Pathways.” PloS one 7.10 (2012): e47516. (PloS one is an open access journal)

Grothey, Axel, and Carmen Allegra. “Antiangiogenesis therapy in the treatment of metastatic colorectal cancer.” Therapeutic Advances in Medical Oncology(2012) (Free PMC article).

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