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The Establishment and Utilization of Patient Derived Xenograft Models of Central Nervous System Metastasis
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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.

EMBO Molecular Medicine
|July 3, 2026
PubMed
Summary

Developing advanced patient-derived resources like organoids and rapid autopsy programs is key to understanding brain metastases (BrM) and improving patient treatment outcomes.

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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.