27.03.2014

The Head of State received the researcher Gabriel Rabinovich and his team

The President received at the Olivos presidential residence the CONICET researcher who discovered with his team a new escape mechanism to the anti - angiogenic treatment of tumors. They were accompanied by the Minister of Science, Lino Barañao.

The President together with Rabinovich during the meeting in Olivos.

The President together with Rabinovich during the meeting in Olivos.

President Cristina Fernández de Kirchner received this afternoon at the Olivos presidential residence the Argentine researcher Gabriel Rabinovich, who together with his team discovered the new escape mechanism to the anti - angiogenic tumor treatment.

"Understanding this mechanism turn sensitive tumors that were previously refractory", Rabinovich explains, "however, further study is still necessary before being applied to patients".

Productive Innovation, Lino Barañao and Economy, Axel Kicillof. Rabinovich, a main researcher of the National Council of Scientific and Technical Research (CONICET), was accompanied by members of his team: Diego Croci, Juan Pablo Cerliani, Mariana Salatino, Marta Toscano, Tomás Dalotto Moreno and Santiago Méndez Huergo, the latter two are fellows of the Council.

The mechanism discovered by Rabinovich discloses the behavior of some tumors resistant to conventional therapies, which could facilitate the future development of more effective cancer treatment therapies.

"Understanding this mechanism turn sensitive tumors that were previously refractory", Rabinovich explains, "however, further study is still necessary before being applied to patients".

His research was published in the cover of the scientific journal Cell.


The Discovery.

The study, conducted at the Institute of Biology and Experimental Medicine (IBYME -CONICET - FIBYME) revealed the nature of one of the mechanisms of tumor resistance of certain types of cancer and the manner to reverse it. The research was published in the prestigious scientific journal Cell as the main article included in that edition's cover.

To understand the research, it is necessary to understand the process by which a tumor is developed. Supply of oxygen and nutrients through blood is essential to ensure the viability of any tissue, but it is very critical to the tumor cells that, due to their high rate of metabolism and reproduction, require higher than normal quantities. Thus, many therapies are aimed at reducing the blood supply to tumors through drugs inhibiting the proliferation of vessels in the area, along with other substances aimed to attack tumors. However, certain tumors do not respond to anti-angiogenic treatments, i.e. those seeking to stop the creation of new vessels, therefore are more difficult to treat.

The key lies in the relationship between two proteins: the Vascular Endothelial Growth Factor (VEGF) and the Galectin-1 (Gal-1). Both molecules, when they act on a specific receptor of VEGF (the VEGFR2), promote the division of endothelial cells to create new blood vessels. Some anti-angiogenic drugs available on the market are specific antibodies acting as “kidnapping” the VEGF and preventing it from binding to its receptor.

"In tumors sensitive to these drugs, the antibody capturing the VEGF has positive effects. But in those resistant to these drugs, shortly after applying, a compensatory mechanism comes into scene triggering the creation of vessels again" says Gabriel Rabinovich, director of the IBYME laboratory of immunopathology.

Rabinovich explained that after 4-5 days of giving the anti-VEGF therapy, the creation of new vessels is stopped and the oxygen levels are decreased. The group found that in refractory tumors the hypoxia activates a cascade of signals leading to the VEGFR2 'undress' of the sialic acid coating. This acid, in normal cells and sensitive tumors, acts as a 'shield' which covers the sites to which the Gal-1 can join, which is also secreted in large amounts by the tumor when the oxygen levels decrease.

Gal-1 acts on the sugars (complex N-glycan) expressing the VEGFR2 of endothelial cells, to which this interaction stimulates to proliferate and form new blood vessels. "In tumors sensitive to the treatment, the sialic acid, normally covering these receptors, remains in the same place. So if Gal-1 has the intention of interacting with receptors, it is impossible. However, in refractory tumors, hypoxia leading to loss of sialic acid and also increases the number of binding sites for this protein" Rabinovich says.

The research team then worked with a group of refractory tumors and managed to reverse sensitivity when giving two antibodies: one 'kidnapping' a VEGF and another one “kidnapping” the Gal-1. "angiogenesis decreases after 7 days from starting the mixed treatment", says Diego Croci, CONICET assistant researcher and first author of the paper, "also, on the 4th. day we noted that the morphology of the tumor vasculature changed". Tumor blood vessels usually have chaotic and heterogeneous layouts, but with the combined therapy vessels reconfigure to resemble normal tissue. This has therapeutic benefits in two aspects: having a more orderly architecture, it has two and three times more oxygen and lymphocytes. Then, by decreasing the levels of hypoxia the Gal- 1 production decreases and the flow of cells of the immune system to fight the tumor increases.

However, the researchers caution that although the results in laboratory and experiment animals are very positive, it is still not available for treatment. "Understanding this mechanism, tumors which were previously refractory turn sensitive", Rabinovich explains, "however, further study is still necessary before being applied to patients".

The research received from 2010 contributions for the amount of $ 1.78 million from the National Agency for Scientific and Technological Promotion under the Ministry of Science, Technology and Productive Innovation and the CONICET, as well as support from the University of Buenos Aires, the Sales Foundation and donations from the Ferioli and Ostry family.

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  • The President together with Rabinovich during the meeting in Olivos.
  • (from left to right) Lic. Sebastián Dergan-Dylon; Santiago Méndez Huergo; Diego Croci; Lino Barañao; Gabriel Rabinovich; Marta Toscano; Tomás Dalotto Moreno; Mariana Salatino; Juan Pablo Cerliani.
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The President together with Rabinovich during the meeting in Olivos.

The President together with Rabinovich during the meeting in Olivos.

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