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Patient-derived resources for decoding and targeting brain metastases ecosystems
Manuel Valiente1, Lal Era Aydoğan2, Nisan Feigin3
1Brain Metastasis Group, Spanish National Cancer Research Centre, Madrid, Spain. mvaliente@cnio.es.
Abstract:
Brain metastases (BrM) affect up to 30% of patients with solid tumors, yet durable intracranial control remains rare, and the biological drivers of this poor prognosis are incompletely understood. Patient-derived resources, such as clinical cohorts, biobanks, functional ex vivo models, and multi-omic platforms, are central to closing this gap, but their generation and integration face substantial logistical and technical hurdles. Drawing on the RISEbrain consortium's experience, this Perspective examines BrM-focused cohorts and biobanks, highlighting the underused potential of rapid autopsy programs to capture early metastatic seeding. We discuss patient-derived organotypic cultures and emerging organoid-based "avatar" systems as functional platforms for therapeutic profiling, alongside the complementary strengths of bulk and single-cell/-nucleus transcriptomics. We outline how spatial transcriptomics and proteomics are resolving the architecture of the BrM microenvironment, and assess liquid biopsy approaches, including emerging photonic biosensors, for non-invasive monitoring. Together, these resources form an interdependent toolkit whose coordinated deployment will advance early detection, prevention, and precision treatment of BrM.
Insights
Developing advanced patient-derived resources like organoids and rapid autopsy programs is key to understanding brain metastases (BrM) and improving patient treatment outcomes.
Area of Science:
- Oncology
- Neuroscience
- Translational Medicine
Background:
- Brain metastases (BrM) occur in up to 30% of cancer patients, with limited treatment options and poor prognosis.
- The biological mechanisms driving BrM and resistance to therapy are not fully understood.
- Existing patient-derived resources face challenges in generation and integration for comprehensive study.
Purpose of the Study:
- To review and highlight the potential of patient-derived resources for advancing brain metastases research.
- To discuss the integration of diverse research tools for improved understanding and treatment of BrM.
- To emphasize the need for coordinated deployment of these resources for clinical impact.
Main Methods:
- Examination of BrM-focused clinical cohorts and biobanks.
- Discussion of rapid autopsy programs for early metastatic seeding analysis.
- Review of ex vivo models including organotypic cultures and organoid "avatar" systems.
- Assessment of multi-omic platforms: bulk and single-cell transcriptomics, spatial transcriptomics, and proteomics.
- Evaluation of liquid biopsy approaches and photonic biosensors for non-invasive monitoring.
Main Results:
- Patient-derived resources, including rapid autopsy programs, offer significant potential for studying early BrM seeding.
- Organoid systems provide functional platforms for therapeutic profiling.
- Multi-omic techniques like spatial transcriptomics and proteomics are elucidating the BrM microenvironment.
- Liquid biopsies show promise for non-invasive monitoring of BrM.
Conclusions:
- Coordinated use of diverse patient-derived resources is essential for advancing brain metastases research.
- These integrated tools can improve early detection, prevention strategies, and precision treatment of BrM.
- Further development and application of these resources hold promise for overcoming the challenges in managing BrM.
