In order for the light to shine so brightly, the darkness must be present: why do cancers fluoresce with 5-aminolaevulinic acid?

Kym McNicholas, Melanie N. MacGregor, Jonathan M. Gleadle

Research output: Contribution to journalReview article

6 Citations (Scopus)
8 Downloads (Pure)

Abstract

Photodynamic diagnosis and therapy have emerged as a promising tool in oncology. Using the visible fluorescence from photosensitisers excited by light, clinicians can both identify and treat tumour cells in situ. Protoporphyrin IX, produced in the penultimate step of the haem synthesis pathway, is a naturally occurring photosensitiser that visibly fluoresces when exposed to light. This fluorescence is enhanced considerably by the exogenous administration of the substrate 5-aminolaevulinic acid (5-ALA). Significantly, 5-ALA-induced protoporphyrin IX accumulates preferentially in cancer cells, and this enhanced fluorescence has been harnessed for the detection and photodynamic treatment of brain, skin and bladder tumours. However, surprisingly little is known about the mechanistic basis for this phenomenon. This review focuses on alterations in the haem pathway in cancer and considers the unique features of the cancer environment, such as altered glucose metabolism, oncogenic mutations and hypoxia, and their potential effects on the protoporphyrin IX phenomenon. A better understanding of why cancer cells fluoresce with 5-ALA would improve its use in cancer diagnostics and therapies.

Original languageEnglish
Pages (from-to)631-639
Number of pages9
JournalBritish Journal of Cancer
Volume121
Issue number8
Early online date13 Aug 2019
DOIs
Publication statusPublished - 15 Oct 2019

Bibliographical note

'This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution 4.0 International (CC BY 4.0).'

Keywords

  • cancer
  • imaging
  • microenvironment
  • metabolism

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