Glycolysis inhibition improves photodynamic therapy response rates for equine sarcoids

Vet Comp Oncol. 2017 Dec;15(4):1543-1552. doi: 10.1111/vco.12299. Epub 2017 Jan 27.

Abstract

Photodynamic therapy (PDT) holds great promise in treating veterinary and human dermatological neoplasms, including equine sarcoids, but is currently hindered by the amount of photosensitiser and light that can be delivered to lesions thicker than around 2 mm, and by the intrinsic antioxidant defences of tumour cells. We have developed a new PDT technique that combines an efficient transdermal penetration enhancer solution, for topical delivery of 5-aminolevulinic acid (ALA) photosensitiser, with acute topical post-PDT application of the glycolysis inhibitor lonidamine. We show that the new PDT combination treatment selectively kills sarcoid cells in vitro, with repeated rounds of treatment increasing sarcoid sensitisation to PDT. In vivo, ALA PDT followed by 600 μM lonidamine substantially improves treatment outcomes for occult, verrucous, nodular and fibroblastic sarcoids after 1 month (93% treatment response in 27 sarcoids), compared with PDT using only ALA (14% treatment response in 7 sarcoids).

Keywords: PDT; combination therapy; glycolysis inhibition; sarcoid; skin; tumour.

Publication types

  • Clinical Trial

MeSH terms

  • Aminolevulinic Acid / therapeutic use*
  • Animals
  • Cell Line, Tumor
  • Glycolysis*
  • Horse Diseases / drug therapy*
  • Horses
  • Photochemotherapy / methods
  • Photochemotherapy / veterinary*
  • Photosensitizing Agents / therapeutic use*
  • Skin Neoplasms / drug therapy
  • Skin Neoplasms / veterinary*

Substances

  • Photosensitizing Agents
  • Aminolevulinic Acid