Researchers at the University of Texas MD Anderson Cancer Center have identified a targetable driver of brain metastases in patients with aggressive inflammatory breast cancer.
The study reveals a novel role for soluble E-cadherin (sEcad) in promoting tumor invasion while resisting cancer cell death and inducing brain inflammation through the CXCR2 signaling pathway. The results suggest that targeting sEcad or the CXCR2 pathway could treat or prevent brain metastasis.
The study, published in Neuro-Oncologyled by Xiaoding Hu, MD, Ph.D., instructor of Breast Medical Oncology, and Bisrat Debeb, DVM, Ph.D., associate professor of Breast Medical Oncology.
This easily measured blood biomarker plays a key role in the induction of brain metastasis. Targeting this pathway has enormous potential for the treatment and prevention of this serious complication and could help guide future therapies.”
Bisrat Debeb, DVM, Ph.D., Associate Professor of Breast Medical Oncology
What prompted researchers’ interest in E-cadherin in brain metastasis?
Brain metastasis is a common complication of advanced breast cancer, with a particularly high risk in inflammatory breast cancer. However, there are no effective treatments because the underlying mechanisms remain poorly understood.
Previous work from the Debeb lab has shown that patients with elevated levels of sEcad in their blood tend to have an increased risk of brain metastasis, early metastasis, and poorer overall survival. Therefore, the researchers wanted to further understand the role of sEcad.
What did the researchers learn in this study?
In this study, preclinical models of inflammatory breast cancer overexpressing sEcad showed higher metastatic burden, decreased survival, and increased brain metastasis. The researchers found that sEcad activates the CXCR2 pathway, which creates a feedback loop that helps cancer cells avoid cell death and encourages an inflammatory, pro-metastatic environment.
Use of a CRCX2 inhibitor significantly reduced metastasis and extended survival in these models, suggesting its potential as a therapeutic target.
What does this mean for patients with inflammatory breast cancer?
This study identifies sEcad and the CRCX2 pathway as key to brain metastasis, suggesting that blocking any part of this pathway could slow or prevent cancer from spreading.
In addition, monitoring blood levels of sEcad could be a way to identify patients at higher risk of brain metastasis, and treatment with a CRCX2 inhibitor appears to be a potential therapeutic strategy for these patients. Further studies are needed to confirm these findings and determine appropriate treatment approaches.
