According to data from the American Cancer Society, pancreatic cancer, common in most developed countries, accounts for about 3% of all cancers in the United States – and about 7% of all cancer deaths. The survival rates are less than 2%, 5 years after diagnosis. The same data shows that the average lifetime risk of developing pancreatic cancer is about 1 in 67 (1.5%). Pancreatic adenocarcinoma is among the most aggressive of all cancers. Because the majority (53%) of all patients newly diagnosed with pancreatic cancer have already disease that has spread to distant sites in the body, and current therapeutic treatment options are relatively ineffective, the identification of new targets is urgently needed.
In Spain 4,000 cases are diagnosed each year. Although it is a tumor that is well known at molecular level, its diagnosis and treatment are still one step behind. In fact it is one of the tumors with the least therapeutic advancements in recent years.
Now researchers from Hospital del Mar Medical Research Institute (IMIM) in Barcelona, Spain, have identified a new protein called galectin-1 that may be a possible therapeutic target for pancreatic cancer. For the first time the researchers have demonstrated the effects of the inhibition of this protein in mice suffering from pancreatic cancer. These results showed an increase in survival of 20%. The work further suggests that it could be a therapeutic target with no adverse effects.
…the reduction of galectin-1 mainly affects the immune system and the cells and structure that surrounds the tumor cells. As a result, this protein may be therapeutic target with great potential…
A better strategy
Until now, the strategies for treating this tumour were aimed at attacking the tumour cells and had little success. The latest studies indicate that trying to destroy what surrounds the tumour is possibly a better strategy. “Our contribution is directed toward this, as the reduction of galectin-1 mainly affects the immune system and the cells and structure that surrounds the tumour cells, which is called the stroma. Therefore, galectin-1 as a therapeutic target has great potential”, explains Pilar Navarro, MD, co-ordinator of the research group on molecular mechanisms of tumorigenesis of IMIM and director of the research.
Gallectin-1
Despite the fact that the protein is strongly expressed in pancreatic tumors, galectin-1 is not found in the normal pancreas. Furthermore, some clear functions were known which demonstrate the relationship between galectin-1 and tumor progression in other contexts. In fact, some preclinical studies for other diseases use inhibitor molecules and antibodies against this protein. “We are aiming at its possible use in pancreatic cancer” states Dr. Neus Mart?nez, researcher of the group on molecular mechanisms and tumorigenesis of IMIM and first author of this article. “We have also observed that the elimination of galectin-1 in mice has no harmful consequences, indicating that it could be a safe therapeutic target with no adverse effects”, she noted.
In collaboration with the Hospital del Mar Anatomical Pathology Service, which has analysed some samples, pancreatic tumors were studied in mice with high levels of galectin-1 and after its depletion. They observed that tumours without this protein showed less proliferation, fewer blood vessels, less inflammation and an increase in the immune response. All these changes are associated with less aggressive tumors.
The results are very encouraging but we must be prudent as there are many factors to take into account. The researchers now want to move the results obtained to preclinical studies, where they will treat mice with pancreatic cancer with chemical inhibitors or antibodies against galectin-1 (the same treatment that would be used for a cancer patient) in order to verify the therapeutic utility of this target. In the event that they obtain positive results and manage to halt the tumour, the next step would be to propose its use on patients. Obviously we are talking about long-term objectives, as the transfer of studies on animals to humans is usually a slow process.
For more information:
Mart?nez-Bosch N, Fern?ndez-Barrena MG, Moreno M, Ortiz-Zapater E, Munn?-Collado J, Iglesias M, Andr? S, Gabius HJ, Hwang RF, Poirier F, Navas C, Guerra C, Fern?ndez-Zapico ME, Navarro P. Galectin-1 Drives Pancreatic Carcinogenesis through Stroma Remodeling and Hedgehog Signaling Activation. Cancer Res. 2014 May 8.[Article][PubMed]
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