Researchers describe a new target for developing anti-angiogenic and anti-tumoral therapies

May 10, 2012

Researchers from the Spanish National Cancer Research Centre (CNIO), led by Jorge L. Martínez-Torrecuadrada from the Proteomics Unit, have demonstrated that the antibody-based blocking of ephrinB2, a protein involved in angiogenesis and lymphoangiogenesis, may represent an effective strategy for the development of antiangiogenic and antitumoural therapies.

The results of this study appeared in this month's issue of Blood, the journal of the American Society of Hematology.

CNIO researchers generated highly-specific human antibodies against ephrin-B2 using a phage display approach. These specific antibodies were able to suppress endothelial cell migration and tube formation in in vitro assays. Also, systemic treatment of mice xenografted with pancreatic, lung or colon carcinoma cells resulted in a significant reduction in the amount of blood and lymphatic vessels.

Concomitantly, a drastic inhibition of the tumour growth was observed in every xenograft mouse model used. Therefore, these results validated ephrinB2 as a potential therapeutic target in tumour angiogenesis and lymphangiogenesis and showed that the ephrinB2-specific antibodies developed in this study may be suitable as leads for the development of new improved antiangiogenic therapies, which can be used alone or can complement or synergise with other established antiangiogenic therapies of application in cancer or other angiogenesis-related pathologies.

The angiogenesis process

Angiogenesis is a complex process by which new blood vascular vessels arise from pre-existing ones. In adulthood and under physiological conditions, this process only occurs in some circumstances, such as wound healing or in the menstrual cycle, but it is also an important factor in several pathologies such as cancer, in which the tumour promotes the formation of new blood vessels. This new vasculature provides the tumour with oxygen and nutrients, allowing these cells to grow, invade nearby tissue and eventually metastasise to distant organs.

In addition to blood vasculature, tumour growth induces the development of lymphatic vessels in a similar process called lymphangiogenesis that plays a key role in tissue–fluid homeostasis, as a tissue-drainage system. Recent studies also demonstrated the critical importance of this lymphatic vasculature for the metastatic spread of tumour cells.

In the last decades, the extensive research in the field of tumour-derived angiogenesis led to the identification of several angiogenic targets that can be effectively blocked in order to prevent the formation of new blood vessels in tumours, starving them of oxygen and nutrients and thereby preventing their growth.

As a result of these researches, several antibodies have been successfully developed and have demonstrated clinical utility in treating several tumour types, such as bevacizumab (Avastin®), which is based on the inhibition of vascular endothelial growth factor (VEGF) that promotes endothelial cell proliferation, migration and differentiation.

However, recent emerging experimental and clinical evidence suggests that tumours treated with this antiangiogenic strategy may eventually develop resistance to therapy and exhibit a progression to greater invasiveness. Therefore, there is a pressing need to explore other angiogenic targets that can be used therapeutically, such as the one validated by CNIO researchers in the study now published in .

Explore further: New strategy to attack tumor-feeding blood vessels

Related Stories

New strategy to attack tumor-feeding blood vessels

June 6, 2011
Scientists at the Walter and Eliza Hall Institute have discovered a key molecule needed to kill the blood vessels that supply tumours.

Recommended for you

Researchers release first draft of a genome-wide cancer 'dependency map'

July 27, 2017
In one of the largest efforts to build a comprehensive catalog of genetic vulnerabilities in cancer, researchers from the Broad Institute of MIT and Harvard and Dana-Farber Cancer Institute have identified more than 760 genes ...

Cancer-death button gets jammed by gut bacterium

July 27, 2017
Researchers at Michigan Medicine and in China showed that a type of bacterium is associated with the recurrence of colorectal cancer and poor outcomes. They found that Fusobacterium nucleatum in the gut can stop chemotherapy ...

Long-sought mechanism of metastasis is discovered in pancreatic cancer

July 27, 2017
Cells, just like people, have memories. They retain molecular markers that at the beginning of their existence helped guide their development. Cells that become cancerous may be making use of these early memories to power ...

Manmade peptides reduce breast cancer's spread

July 27, 2017
Manmade peptides that directly disrupt the inner workings of a gene known to support cancer's spread significantly reduce metastasis in a mouse model of breast cancer, scientists say.

Blocking the back-door that cancer cells use to escape death by radiotherapy

July 27, 2017
A natural healing mechanism of the body may be reducing the efficiency of radiotherapy in breast cancer patients, according to a new study.

Glowing tumor technology helps surgeons remove hidden cancer cells

July 27, 2017
Surgeons were able to identify and remove a greater number of cancerous nodules from lung cancer patients when combining intraoperative molecular imaging (IMI) - through the use of a contrast agent that makes tumor cells ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.