Rethinking metastatic brain cancer as a central nervous system disease

A Personal View published in The Lancet Oncology challenges the long-standing perception of metastatic brain cancer, calling to recognize it as a distinct central nervous system (CNS) disease rather than a mere extension of its primary tumor.

The perspective, led by Jawad Fares, MD, along with colleagues from Northwestern University, highlights the unique molecular, genetic, and microenvironmental features of brain metastases that distinguish them from their systemic origins.

“For decades, metastatic brain cancer has been treated as an afterthought, managed primarily within the context of its primary tumor,” said Dr. Fares, a resident neurosurgeon and physician-scientist at Northwestern University Feinberg School of Medicine.

“However, our growing understanding of the biology of these tumors suggests that they should be classified and studied as a CNS disease. This shift in perspective is not just a semantic one—it has profound implications for research funding, clinical trial design, and ultimately, patient outcomes.”

The perspective argues that metastatic brain cancer has distinct biological characteristics that set it apart from its primary tumor, including adaptations that allow tumor cells to cross the blood-brain barrier, evade immune surveillance, reprogram astrocytes, and alter metabolic pathways to sustain their survival in the brain’s unique environment.

These insights challenge the conventional treatment approach, which often mirrors systemic cancer therapies rather than focusing on the specific vulnerabilities of brain metastases.

Dr. Fares and his co-authors emphasize that the failure to recognize metastatic brain cancer as a CNS disease has led to a lack of dedicated research and clinical trials tailored to its unique biology.

“Currently, many trials exclude patients with brain metastases, limiting the development of therapies that specifically target these tumors,” he said. “If we continue to view brain metastases only through the lens of their primary cancer, we risk missing critical opportunities for advancing treatment.”

The authors call for a paradigm shift in research priorities, urging increased funding, biomarker-driven studies, and the development of CNS-specific therapeutic strategies. By treating brain metastases as a primary focus rather than a secondary concern, the medical community can drive innovations that improve both survival and quality of life for patients facing this devastating disease.

“This is a call to action,” said Dr. Fares. “If we redefine metastatic brain cancer as a CNS disease, we can accelerate the development of precision medicine approaches, enhance clinical trial design, and, most importantly, offer better hope to patients.”