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AACR 2018 Highlights: Novel Approaches to Treating Brain Metastasis in Metastatic Breast Cancer
BCRF investigators try to understand the brain’s unique environment to prevent and treat brain metastasis.
Metastasis occurs when a cancer cell leaves the tissue from which it originated and forms a new tumor in a different organ. When breast cancer spreads to the brain, known as brain metastasis, few treatment options exist. It’s a challenge that several BCRF investigators are trying to overcome with their research projects.
“Brain metastasis is the final frontier in oncology and an enormous unmet need,” BCRF researcher Dr. Priscilla Brastianos told BCRF at the AACR Annual Meeting where she gave a talk on the tumor biology of brain metastasis.
While there is no cure for metastatic breast cancer (MBC), new treatments such as CDK 4/6 inhibitors, PARP inhibitors and novel combination therapies are extending the lives of many patients with MBC. However, no such advances have arrived for breast cancers that have spread to the brain.
Dr. Brastianos is one BCRF investigator dedicated to finding a way to prevent and treat brain metastasis. Breast cancer that spreads to the brain accounts for approximately 30 percent of MBC in patients with HER2-positive breast cancer and about 50 percent of MBC in patients with triple negative breast cancer – yet most of these patients are excluded from clinical trials.
A challenge for clinical trials
One of the challenges in conducting clinical trials for patients with brain metastasis is the lack of drugs that penetrate the blood-brain barrier – a selective semipermeable membrane that separates circulating blood from the brain.
Dr. Brastianos’ work is focused on finding new targets that will lead to better treatment approaches.
In search of these targets, Dr. Brastianos’ team compares changes in gene expression in tumor cells from the primary breast cancer to those in the brain metastasis. Her work has shown that tumor cells evolve during the development of metastasis and acquire unique gene mutations that may be targets for drug development.
Finding new treatment targets
In over half of the brain metastases she has studied, her team found clinically actionable mutations that were not found in the primary cancer. Based on these findings, she and her colleagues have initiated clinical trials to see if targeting these alterations can improve patient outcomes.
Another approach to preventing brain metastasis is to identify patients at risk of brain metastasis before it occurs. BCRF investigator Sofia Merajver and her colleagues have developed a device that mimics the brain niche – the microenvironment of the brain – to study how and why tumor cells from the breast form new tumors in the brain.
Dr. Ryan Oliver, an engineer working with Dr. Merajver, presented this model at the AACR Annual Meeting. He explained to BCRF that the device allows researchers to study which cells from the primary breast tumor are able to cross the blood-brain barrier. They hope this inexpensive laboratory test can be used in the clinic to identify newly diagnosed breast cancer patients who are at risk of brain metastasis.
Facebook Live interviews at the AACR Annual Meeting
To learn more about these exciting BCRF projects, watch the complete interviews with Dr. Brastianos and Dr. Ryan below: