The University of Florence researchers, in collaboration with London’s Institute of Cancer Research, have uncovered a potential cause of sustained resistance to hormone therapy in the most common form of breast cancer. The findings could help us someday find new treatments to overcome hormone-resistant breast cancer.
Hormone therapy represents an effective treatment for the majority of breast cancers that are hormone receptor-positive—those cancers that have an estrogen receptor on the surface of the cells. However, 40% of women relapse with a form of the disease, which often becomes resistant to available treatments, which can become dangerous.
Breast Cancers Seek to Survive
Researchers, not those breast cancers which become resistant to hormone therapy, possess a molecular advantage aiding their cells to evade hormone therapies successfully. Unfortunately, these hormone therapies represent the best treatment options currently available for patients with hormone receptor-positive (or ER+) cancers.
The Anglo/Italian Breakthrough
The investigators from the UK and central Italy revealed that those breast cancer cells that exhibit resistance to hormone therapy possess more of the microRNA molecule known as miR-23b-3p. As it turns out, miR23-3p promotes a decrease in a type of protein for transporting amino acids, which are either alkaline or neutral in pH. Somehow in these situations, a rise is seen in a different kind of transporter dealing with amino acids—glutamate and aspartate. So cells that are reliant on acidic amino acids now can successfully resist hormone therapy treatment.
Published in Cell Reports, the researchers exploited multiple models of cancer, including patient-derived xenografts—those that originate from a patient but after that are implemented into a mouse model to aid the studying and monitoring of the condition. The team was able to closely watch the naturally growing cancers and collect essential data regarding each original patient.
So as the scientists studied each gene expression in the cancer cells, they developed the ability to identify which substances were produced in excess and which elements were produced in fewer amounts.
Finally, the team was able to understand better which molecules the cancer cells were reliant on as fuel sources and which substances the cells were not able to exploit. For example, those cells unable to transport neutral and essential amino acids became forced to rely on their acidic counterparts.
Results and Discussion
The team revealed that by boosting the amounts of aspartate and glutamate in ER+ breast cancer cells was linked to the development of resistance to endocrine therapy. Fascinatingly, by shutting off the cells’ ability to move aspartate and glutamate inside the cell reduced the ability of endocrine therapy-resistant cells to spread—this appears to be proof to the scientists that a robust relationship exists between these molecules and the cancer cells’ ability to survive and thrive reported The Institute for Cancer Research.
Dr. Andrea Morandi, Assistant Professor of Biochemistry and Group Leader University of Florence
Call to Action: For those translational researchers following TrialSite News, we will continue to track this ICR and University of Florence group, including Dr. Morandi. They are hoping to use future research to offer more valuable predictive information as to the likelihood of relapse in patients with hormone therapy-resistant cancers—with the ultimate goal of searching for new methods to target these cancers.