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Published on: February 8, 2017
Rethinking metastatic brain cancer as a CNS disease
Jawad Fares1, Edgar Petrosyan1, Crismita Dmello1
1Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA; Northwestern Medicine Malnati Brain Tumor Institute, Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Abstract:
Advances in molecular biology, genetics, and epigenetics have refined our understanding of metastatic brain cancer and underscored the need for better classification and targeted approaches. The heterogeneity of brain metastases highlights the differences from their primary source of origin and contributes to therapeutic resistance. Before colonising the brain, tumour cells acquire specialised proficiencies that enable them to capitalise on the unique microenvironment of the brain. The tumour cells further orchestrate key adaptations to adjust to the brain microenvironment by manipulating the blood-brain barrier, evading immune surveillance, rewiring metabolic profiles, and reprogramming astrocytes. These adaptations facilitate tumour survival, growth, and treatment resistance. Recognising metastatic brain cancer as a distinctive CNS disease, rather than an extension of the primary cancer, would support the development of rational approaches that target its molecular and genetic features and improve research funding in this area. Here, we delve into the distinct genetic and phenotypic characteristics of metastatic brain cancer, and reflect on how a change in the perception of this disease could accelerate the development of more effective therapies and drive continued progress in the field of neuro-oncology.
Insights
Metastatic brain cancer exhibits unique genetic and phenotypic traits, differing significantly from primary tumors. Recognizing it as a distinct CNS disease is crucial for developing targeted therapies and improving patient outcomes.
Area of Science:
- Neuro-oncology
- Molecular Biology
- Cancer Genetics
Background:
- Advances in molecular biology, genetics, and epigenetics have improved understanding of brain metastases.
- Brain metastases are heterogeneous, differing from primary tumors and contributing to therapeutic resistance.
- Tumor cells acquire specialized proficiencies to adapt to the brain microenvironment before colonization.
Purpose of the Study:
- To explore the distinct genetic and phenotypic characteristics of metastatic brain cancer.
- To advocate for recognizing metastatic brain cancer as a distinct Central Nervous System (CNS) disease.
- To accelerate the development of more effective therapies through a paradigm shift in disease perception.
Main Methods:
- Review of current literature on molecular biology, genetics, and epigenetics of brain metastases.
- Analysis of tumor cell adaptations to the brain microenvironment, including blood-brain barrier manipulation, immune evasion, metabolic rewiring, and astrocyte reprogramming.
- Comparative analysis of brain metastases versus primary tumors.
Main Results:
- Brain metastases possess unique genetic and phenotypic characteristics, distinguishing them from their primary origin.
- Tumor cells undergo specific adaptations to survive, grow, and resist treatment within the brain microenvironment.
- Current classification may hinder the development of targeted therapies.
Conclusions:
- Metastatic brain cancer should be recognized as a distinct CNS disease.
- This reclassification can foster the development of rational, targeted therapeutic approaches.
- A shift in perspective is essential for advancing neuro-oncology and improving treatment efficacy.
