ReviewNeuro-oncology2026
5-Aminolevulinic acid-mediated protoporphyrin IX accumulation in the tumor microenvironment of glioma and its implications for 5-aminolevulinic acid-based local tumor therapies: A review of the literature.
Review in Neuro-oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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4 authors.
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Abstract
5-Aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) accumulation is widely used for fluorescence-guided surgery in malignant glioma. Beyond its diagnostic role, PpIX exhibits photo-, sono-, and radiosensitizing properties that enable locally applied tumor therapies. For these modalities, the cellular and subcellular localization of PpIX is a critical determinant of therapeutic efficacy, as it defines the site of reactive oxygen species generation and subsequent biological effects. In this comprehensive literature review, the cellular and subcellular distribution of 5-ALA-induced PpIX in gliomas and their tumor microenvironment (TME) was assessed. Studies were identified through a structured MEDLINE search and evaluated for evidence of PpIX localization in neoplastic and nonneoplastic cellular components. Accumulating data indicate that PpIX localizes not only within malignant glioma cells but also across multiple cellular components of the TME. Advanced imaging, single-cell, and spatial transcriptomic analyses demonstrate PpIX fluorescence frequently aligns with immunosuppressive myeloid populations and infiltrative tumor regions. Subcellularly, PpIX localizes in mitochondria, lysosomal-autophagic compartments, and extracellular structures, in a cell-type dependent manner. These distribution patterns provide a biological basis for the immunomodulatory, antiangiogenic, and cytotoxic effects observed in studies of 5-ALA-mediated local therapies. While macroscopic fluorescence remains clinically valuable for fluorescence-guided resection, the biologically relevant microscopic distribution of PpIX supports the concept that PpIX-based therapies may target not only tumor cells but also immunosuppressive and stromal compartments. A refined understanding of PpIX localization is therefore central to optimizing nonsurgical 5-ALA-based therapies and their integration into multimodal glioma treatment paradigms.
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