The investigation arose from a clinical need, explained Atanasio Pandiella, director of research, told DiCYT. “There is a subgroup of patients with breast cancer with high expression of a protein called HER2. These patients are treated with a drug called Herceptin. However, this treatment is effective only in a certain percentage of patients who have over expression of HER2, so not all patients respond well, “he says. In addition, relapses occur frequently, the disease recurs, so that the effectiveness of the drug is very low.
Therefore, the research group Pandiella decided to try a combination of Herceptin with new-generation drugs to find a more satisfying. “We tested a list of more than 20 drugs and all of them, gave a good result Dasatinib, which is approved for leukemia and chronic amyloid. When combined with Herceptin makes the antitumor effect is much stronger than the individual effect of each of the drugs, “he says.
Herceptin is a monoclonal antibody that recognizes HER2, a protein found in the cell membrane, exposed on the surface, so that the drug attacks the cells with high expression of HER2.
For its part, Dasatinib is based on smaller molecules that are inhibitors of kinases and are able to enter the cell and act on several cellular kinases, but not on Her2, which is also.
“The combination of multiple kinase inhibitors led to a much more remarkable than the individual effect of each of these drugs,” says Pandiella. We saw both cell lines and generated tumors in experimental animals. Moreover, “in some animals the tumor came to disappear and did not return even after treatment withdrawal.”
How the combination
Why is it so different from the treatment with a single drug and combined? “The biggest difference we have found we are concerned that this combination treatment causes the tumor cell DNA damage,” he explains. The DNA is broken and the tumor cell can not repair, which is not true when applied only one drug alone.
“This causes the cell damage that can not repair it so we die and shrink tumors. We’re not just stopping the tumor to keep growing, which is the effect of Herceptin, but it shrinks because it kills cells tumor, “he adds.
Now, the Spanish Group for Breast Cancer Research (GEICAM) will test the new treatment in patients in Spain, including the Department of Oncology, University Hospital of Salamanca. If the results are as good as in animal models, the jump that will have been in the treatment of breast cancer is very important because at present Herceptin fails in two out of three patients. In addition, you can not tell whether a patient will respond well to treatment.
“Now is given to all patients with HER2 over expression,” says the researcher, who has also launched a line of research to try to find out why some patients respond and others do not. “If we identify that we will not respond a triple benefit “to avoid unnecessary toxicity, opening the possibility for treatment with other drugs and save money by not having to use Herceptin.
The results of this research has been published in The Journal of the National Cancer Institute, responded to three years of work. “After the first hard data, which appeared two years, we talked to GEICAM, and began to develop a protocol for clinical trial with this combination. The trial is approved and this is one of the most rewarding for us, that work you do in the laboratory reach patients, “said Pandiella.
The investigation also participated Samuel Seoane and Juan Carlos Montero, laboratory scientists Pandiella and Alberto Ocaña, researcher of Oncology Unit of the Spanish Association against Cancer Albacete.