Molecular and metabolic mechanisms underlying selective 5-aminolevulinic acid-induced fluorescence in gliomas

Jeffrey I. Traylor, Mark N. Pernik, Alex C. Sternisha, Samuel K. McBrayer, Kalil G. Abdullah

Research output: Contribution to journalReview articlepeer-review

Abstract

5-aminolevulinic acid (5-ALA) is a porphyrin precursor in the heme synthesis pathway. When supplied exogenously, certain cancers consume 5-ALA and convert it to the fluorogenic metabolite protoporphyrin IX (PpIX), causing tumor-specific tissue fluorescence. Preoperative administration of 5-ALA is used to aid neurosurgical resection of high-grade gliomas such as glioblastoma, allowing for increased extent of resection and progression free survival for these patients. A subset of gliomas, especially low-grade tumors, do not accumulate PpIX intracellularly or readily fluoresce upon 5-ALA administration, making gross total resection difficult to achieve in diffuse lesions. We review existing literature on 5-ALA metabolism and PpIX accumulation to explore potential mechanisms of 5-ALA-induced glioma tissue fluorescence. Targeting the heme synthesis pathway and understanding its dysregulation in malignant tissues could aid the development of adjunct therapies to increase intraoperative fluorescence after 5-ALA treatment.

Original languageEnglish (US)
Article number580
Pages (from-to)1-15
Number of pages15
JournalCancers
Volume13
Issue number3
DOIs
StatePublished - Feb 1 2021

Keywords

  • 5-ALA
  • High-grade glioma
  • Intraoperative fluorescence
  • Low-grade glioma
  • Protopor-phyrin IX

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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