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Proceedings Paper

5-Fluorouracil as an enhancer of aminolevulinate-based photodynamic therapy for skin cancer: New use for a venerable agent?
Author(s): Edward V. Maytin; Sanjay Anand; Clara Wilson; Karthik Iyer
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Paper Abstract

5-Fluorouracil (5-FU) was developed in the 1950s as an anticancer drug and is now widely used to treat many cancers, including colon and breast carcinoma. 5-FU causes fluoronucleotide misincorporation into RNA and DNA, inhibits thymidylate synthase, and leads to growth arrest and apoptosis. For skin precancers (actinic keratoses; AK), 5-FU is prescribed as a topical agent and was essentially the only option for treating widespread AK of the skin prior to FDA approval of photodynamic therapy (PDT) in 1999. PDT is now gradually replacing 5-FU as a preferred treatment for AK, but neither PDT nor 5-FU are effective for true skin cancers (basal or squamous cell), particularly for tumors >1 mm in depth. In our ongoing work to improve the efficacy of PDT for skin cancer, we previously showed that PDT efficacy can be significantly enhanced by preconditioning tumors with methotrexate (MTX), which leads to increased production of protoporphyrin IX (PpIX) in target cells. However, because MTX must be given orally or intravenously, it is considered unacceptable for widespread human use due to potential toxicity. MTX and 5-FU exert similar effects on the thymidylate synthesis pathway, so we reasoned that topical 5-FU could be a potential alternative to MTX. In this paper, exploratory studies that test 5-FU as a preconditioning agent for PDT are presented. In a cutaneous model of squamous cell carcinoma (chemically-induced papillomatous tumors in mice), 5-FU significantly enhances PpIX accumulation and therefore emerges as a new candidate agent for combination therapy with PDT.

Paper Details

Date Published: 10 February 2011
PDF: 8 pages
Proc. SPIE 7886, Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XX, 78860K (10 February 2011); doi: 10.1117/12.874188
Show Author Affiliations
Edward V. Maytin, The Cleveland Clinic (United States)
Sanjay Anand, The Cleveland Clinic (United States)
Clara Wilson, The Cleveland Clinic (United States)
Karthik Iyer, The Cleveland Clinic (United States)

Published in SPIE Proceedings Vol. 7886:
Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XX
David H. Kessel; Tayyaba Hasan, Editor(s)

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