In clinical pathology, a triple-negative diagnosis means breast cancer cells have tested negative for estrogen receptors (ER-), progesterone receptors (PR-), and HER2 (HER2-). If you aren’t familiar with what this means, you are certainly not alone. So let’s break things down and talk about why it’s important.
The most common breast cancers possess one or more of the aforementioned hormone receptors and can be treated using hormonal therapy in addition to radiation therapy. However, about 10-20% of all breast cancers are triple-negative and that fact comes with an unfortunate realization: treatment options are significantly limited and the lack of targeted therapies leads to a disproportionally high mortality rate. For researchers, a better understanding of this cancer and more accurate detection tests are top priorities.
A team comprised of scientists from the Van Andel Research Institute and Wayne State University has been studying potential targeted treatments for the lethal cancer. Their new paper, Cabozantinib (XL184) inhibits growth and invasion of preclinical TNBC models, announces a potential breakthrough treatment with a known drug.
The MET protein, also known as the hepatocyte growth factor receptor, drives many of the processes which make cancer dangerous, invasive, and aggressive. Under normal conditions, MET is only expressed by stem cells and progenitor cells. It allows them to grow rapidly to create new tissue or to regenerate damaged tissue. Cancer cells hijack MET expression to grow and move about. Overexpression of MET is found in 20-30% of all breast cancer types.
In promising preclinical trials, the research team demonstrated that the drug cabozantinib successfully inhibited growth in a number of triple-negative breast cancer types by attacking expression of the MET protein. A previous study identified the MET protein as a potential target in treatment therapies of triple-negative breast cancer. Cabozantinib is currently approved to treat metastatic medullary thyroid cancer.
VARI scientist and corresponding author Carrie Graveel is “hopeful that these discoveries will lead to new treatments for patients battling these tough-to-treat cancers” should clinical trials showcase the same success as the preclinical trials.
For those interested in the nuts and bolts of the preclinical research; senior author, Dr. Bonnie Sloane of Wayne State University, explains that their research built mathematical models to mimic the interaction between the drug and the cancer cells while taking into account the surrounding area of the cancer and how that plays a role in the growth of the cancer.
- Photo Credit: Van Andel Institute