A new approach that mimics the body's natural defense mechanisms may lead to the treatment of a type of breast cancer that shows resistance to drugs.
Anticancer drugs of the new molecular generation attack breast cancer in a targeted way: they block molecules characteristic of the malignant tumor cells, namely, receptors for the hormones estrogen and progesterone, as well as the receptor called 2HER, which binds to many growth factors. However, about one in six malignant breast tumors does not contain any of these receptors. Tumors of this type, called "triple-negative", are particularly aggressive and resistant to treatment.
In some of these cancers there is another possible molecular target, a receptor that binds to a growth factor called EGFR, but drugs that inhibit EFGR have not been useful in the treatment of triple-negative cancer. In a study recently published in the scientific journal Proceedings of the National Academy of Sciences, Weizmann Institute of Science scientists offer a possible solution: treating triple-negative breast cancer using two antibodies that inhibit EGFR, instead of one. A combination of two certain antibodies did prevent the growth and spread of these tumors in mice. The research group, led by Prof. Yosef Jordan from the Department of Biological Control and Prof. Michael Sela from the Department of Immunology, included Dr. Daniela Ferraro, Dr. Nadaz Gaborit, Dr. Ruth Maron, Dr. Hadas Cohen-Dabashi, Dr. Ziv Porat, Dr. Persia Parcha, Sara Lavi, Dr. Moshit Lindzen and Nir Ben Shtrit.
The scientists tried several combinations of antibodies and found that the treatment worked when the two antibodies bound to different parts of the EGFR receptor. The combined effect of the two antibodies was greater than would be expected from the sum of the separate effects of each. The use of two antibodies seems to have created a whole new mechanism of blocking the cancer: the antibodies not only inhibited the EGFR, and not only called in the help of immune cells, but also apparently caused the EGFR to collapse under their weight, so that the receptor was swallowed from the cell membrane into it. As a result, without EGFR on the surface, the cells stopped receiving the growth signals, and the growth of the cancerous tumor was prevented. This approach is reminiscent of the natural function of the immune system, which tends to block important antigens at several binding sites with the help of many antibodies.
In the future, the two-antibody method, combined with chemotherapy, may lead to the development of an effective treatment against triple-negative breast cancer.
