90% of breast cancer deaths are due to complications derived from metastasisa process in which cancer cells break away from the area where they formed and reach other parts of the body traveling through the blood or lymphatic circulatory system, forming new tumors.
Now, the Azrieli Faculty of Medicine at Bar-Ilan University in Israel has discovered a new molecular blocker that slows the spread of cancer.
When the researchers began the study about four years ago, they discovered two important clues to the formation of invadepodiafoot-shaped protrusions that degrade the underlying tissue and enter the bloodstream forming metastases: the cellular level of the Pyk2 and cotactin proteins increased suspiciously when the cell entered its malignant phase and, on the contrary, it lost its ability to produce Pyk2 when no metastasis was observed.
For this reason, research has characterized the relationship of associated proteins, demonstrating that the interaction between them is a prerequisite for the formation of cancer cell metastases.
In the study, the precise segment of the protein that was involved in the interaction of Pyk2 and cortactin was defined, called a peptide, which was synthesized in the laboratory and administered to mice bearing breast cancer. this segment competed with the Pyk2 protein for cortactin’s attention successfully and blocked Pyk2’s access to it by inhibiting the formation of leg-like inadopodia and as a result, the mice’s lungs remained healthier, with very few metastases. All of this was achieved with a very small segment of Pyk2 encompassing only 19 of the 1,0009 amino acid building blocks.
“We were excited to see that the idea of using the cortactin-binding motif of Pyk2 as an inhibitor of invadopodia worked quite well in vivo. This served to demonstrate the clinical potential of inhibiting the newly discovered interaction.“said study co-author Dr. Hava Gil-Henn.
The invasiveness of breast tumors was also greatly reduced, the maturation of invadopodia in tumor cells was arrested, and the rate of actin polymerization, necessary for the progression of lump formation, was decreased. All this demonstrating that the 19 amino acid peptide actually blocks metastasis.
“The process of developing a successful drug from an inhibitory peptide is extremely demanding and almost impossible to complete without a structural insight into the complex between the peptide and its target, in this case cortactin,” commented one of the authors, Jordan Chill.
Now, researchers seek to transform the peptide into a better drug candidate, testing different amino acid sequences to obtain a product that binds stronger and more specifically at the cortactin target site. It’s important to nail down where the cortactin attaches because it’s similar to other attachments and getting it wrong can lead to side effects.
the researchers they hope that this advance will lead to the development of a drug that inhibits the formation of metastases and become part of therapeutic approaches to improve the chances of survival and quality of life for patients diagnosed with invasive breast cancer and other metastatic cancers.
