TEL AVIV, February 29, 2024 – A newly discovered mechanism explains how breast cancer spreads to the brain, a especially deadly growth with limited treatment options. The international research, published today, offers a potential pathway for new drugs and more personalized monitoring to catch thes metastases early.
understanding the Deadly Spread
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Brain metastases are among the moast challenging to treat and contribute significantly to cancer-related deaths.
- Researchers pinpointed a chromosomal alteration linked to increased brain metastasis risk.
- Loss of the p53 gene allows cancer cells to thrive in the brain’s unique surroundings.
- Inhibiting the SCD1 enzyme shows promise in slowing metastasis development.
- Identifying high-risk patients early could refine treatment strategies.
Most cancer deaths aren’t caused by the original tumor, but by its spread-metastasis-to vital organs. This study, appearing in the journal Nature cancer, focuses on breast cancer, which frequently metastasizes to the brain.
“We discovered that the absence of a functional p53 gene is essential for the formation and proliferation of cancerous brain metastases,” said Dr. Ben-David, lead researcher on the study.”Experiments in mice showed that cancer cells lacking functional p53 thrived in the brain, while those with it did not.”
Adapting to a New Environment
The brain presents a drastically different environment than the breast, where the primary tumor originates.Professor Ronit Satchi-Fainaro explained, “The question is how a breast cancer cell, adapted to its original environment, can adapt to this foreign environment. According to our findings,this adaptation is closely related to the alteration of the p53 gene.”
The altered p53 gene impacts fatty acid synthesis, a critical metabolic process in the brain. “This means that cells with damaged p53 or no p53 at all produce more fatty acids compared to normal cells, which in turn allows them to grow and divide more quickly in the brain,” Satchi-Fainaro said.
Specifically, cancer cells without functional p53 hijack substances secreted by astrocytes-brain cells-to fuel fatty acid production. Researchers identified a key enzyme in this process, SCD1, which showed significantly higher expression and activity in cancer cells with damaged or absent p53.
New Drug Targets on the horizon
Now that the mechanism is understood, researchers are focusing on potential drug targets.”Once the mechanism and its key factors have been identified, we seek to use the findings to search for a possible drug against brain metastases,” Ben David said. “We focus on the enzyme SCD1 and we evaluate the effectiveness of several drugs that inhibit its activity and that are currently in development.”
Initial tests of SCD1 inhibitors,originally developed for other conditions,proved effective in hindering the development and proliferation of cancerous metastases in both mice and samples from women with breast cancer.
Personalized Monitoring and Treatment
The findings also have implications for patient care. identifying p53 mutations-or deletions on the short arm of chromosome 17-early in breast cancer diagnosis could help doctors predict the risk of brain metastases. This could lead to avoiding aggressive treatments for low-risk patients and prioritizing aggressive treatment for those at higher risk.
Doctors could also tailor monitoring schedules, performing frequent brain mris on patients identified as high-risk. Early detection through intensive monitoring could significantly improve recovery chances.
“In this study, we join forces in a broad international effort to address a crucial question: What is the mechanism that allows breast cancer to metastasize to the brain? We identify several characteristics of cancer cells causally related to this deadly phenomenon,” the researchers highlighted. “Furthermore, our findings are expected to improve the ability of oncologists to identify high-risk patients and prepare appropriately.Although the road ahead is still long, the potential is immense.”
