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Minimally Invasive Cisterna Magna Injection Model for Leptomeningeal Metastasis Studies in Mice
Published on: May 23, 2025
Emerging innovative treatments for leptomeningeal metastatic tumors
Nobuhiko Kanaya1, Khalid Shah2
1Center for Stem Cell and Translational Immunotherapy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama 700-8558, Japan.
Abstract:
Leptomeningeal metastasis (LM) represents a devastating and terminal complication of advanced solid tumors, characterized by the dissemination of malignant cells within the leptomeninges and cerebrospinal fluid. Conventional therapies have demonstrated limited efficacy due to substantial toxicity and poor drug penetration. Recent advances in targeted therapy, immunotherapy, and intrathecal drug delivery are reshaping the therapeutic landscape for LM. Brain-penetrant agents have shown improved outcomes, and intrathecal administration of antibodies and immune checkpoint inhibitors (ICIs) further expands therapeutic options. Immunotherapies, notably chimeric antigen receptor T cells (CAR-T cells) and mesenchymal stem-cell-based therapies offer promise in counteracting LM's immunosuppressive microenvironment. These innovations represent a paradigm shift in the management of LM and offer a renewed therapeutic potential for patients with LM. This review highlights key preclinical and clinical advances that are reshaping the management of LM.
Insights
Leptomeningeal metastasis (LM) treatments are improving with targeted therapies, immunotherapies, and advanced drug delivery. These innovations offer new hope for patients with this advanced cancer complication.
Area of Science:
- Oncology
- Neurology
- Cancer Research
Background:
- Leptomeningeal metastasis (LM) is a severe complication of advanced solid tumors.
- Current treatments for LM have limited efficacy and significant toxicity.
- Poor drug penetration into the central nervous system hinders conventional therapy.
Purpose of the Study:
- To review recent advances in the management of leptomeningeal metastasis.
- To highlight novel therapeutic strategies and their clinical impact.
- To discuss the evolving landscape of LM treatment.
Main Methods:
- Review of preclinical and clinical studies on LM therapies.
- Analysis of advancements in targeted therapy, immunotherapy, and drug delivery.
- Examination of novel agents and treatment modalities.
Main Results:
- Brain-penetrant agents demonstrate improved outcomes in LM.
- Intrathecal administration of antibodies and immune checkpoint inhibitors (ICIs) expands treatment options.
- Immunotherapies like CAR-T cells and stem cell therapies show promise against LM's microenvironment.
Conclusions:
- Recent innovations are transforming LM management.
- New therapeutic approaches offer renewed potential for LM patients.
- The review underscores a paradigm shift in treating leptomeningeal metastasis.
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