ArticleMolecular cancer therapeutics2017
Fluorouracil Enhances Photodynamic Therapy of Squamous Cell Carcinoma via a p53-Independent Mechanism that Increases Protoporphyrin IX levels and Tumor Cell Death.
Article in Molecular cancer therapeutics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 57 citations in OpenAlex.
- Photodynamic Evaluation of Synthesized Chlorin-Desthiobiotin Conjugate with Chemotherapeutic Drugs in Triple-Negative Breast Cancer Cells In Vitro and in Hydra Organisms In Vivo.International journal of molecular sciences · 2025Article
- Photosensitized Oxidative Damage from a New Perspective: The Influence of Before-Light and After-Light Reaction Conditions.The Journal of organic chemistry · 2024Review
- Photodynamic Therapy in the Treatment of Cancer-The Selection of Synthetic Photosensitizers.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Cutaneous Squamous Cell Carcinoma: An Updated Review.Cancers · 2024Review
- Comparative response to PDT with methyl-aminolevulinate and temoporfin in cutaneous and oral squamous cell carcinoma cells.Scientific reports · 2024Article
- The use of photodynamic therapy in medical practice.Frontiers in oncology · 2024Review
- The m-TORC1 inhibitor Sirolimus increases the effectiveness of Photodynamic therapy in the treatment of cutaneous Squamous Cell Carcinoma, impairing NRF2 antioxidant signaling.International journal of biological sciences · 2024Article
- Topical N-phosphonacetyl-l-aspartate is a dual action candidate for treating non-melanoma skin cancer.Experimental dermatology · 2023Article
- Sustained resolution of nonmelanoma skin cancer with photodynamic therapy using 10% 5-aminolevulinic acid hydrochloride gel: A retrospective case series.JAAD case reports · 2023Article
- Combination of 5-Fluorouracil with Photodynamic Therapy: Enhancement of Innate and Adaptive Immune Responses in a Murine Model of Actinic KeratosisPhotochemistry and photobiology · 2023Review
- Global Trends and Research Progress of Photodynamic Therapy in Skin Cancer: A Bibliometric Analysis and Literature Review.Clinical, cosmetic and investigational dermatology · 2023Review
- Article
- The cell-line-derived subcutaneous tumor model in preclinical cancer research.Nature protocols · 2022Review
- Supramolecular co-encapsulation of a photosensitizer and chemotherapeutic drug in cucurbit[8]uril for potential chemophototherapy.Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology · 2022Article
- The Immunogenetic Aspects of Photodynamic Therapy.Advances in experimental medicine and biology · 2022Article
- Painless Photodynamic Therapy Triggers Innate and Adaptive Immune Responses in a Murine Model of UV-induced Squamous Skin Pre-cancer.Photochemistry and photobiology · 2021Article
- The Assessment of the Combined Treatment of 5-ALA Mediated Photodynamic Therapy and Thalidomide on 4T1 Breast Carcinoma and 2H11 Endothelial Cell Line.Molecules (Basel, Switzerland) · 2020Article
- Photodynamic Diagnosis and Therapy for Peritoneal Carcinomatosis: Emerging Perspectives.Cancers · 2020Review
- Vitamin D and Other Differentiation-promoting Agents as Neoadjuvants for Photodynamic Therapy of Cancer.Photochemistry and photobiology · 2020Review
- A promising anticancer drug: a photosensitizer based on the porphyrin skeleton.RSC medicinal chemistry · 2020Review
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Photodynamic therapy (PDT), using 5-aminolevulinic acid (ALA) to drive synthesis of protoporphryin IX (PpIX) is a promising, scar-free alternative to surgery for skin cancers, including squamous cell carcinoma (SCC) and SCC precursors called actinic keratoses. In the United States, PDT is only FDA approved for treatment of actinic keratoses; this narrow range of indications could be broadened if PDT efficacy were improved. Toward that goal, we developed a mechanism-based combination approach using 5-fluorouracil (5-FU) as a neoadjuvant for ALA-based PDT. In mouse models of SCC (orthotopic UV-induced lesions, and subcutaneous A431 and 4T1 tumors), pretreatment with 5-FU for 3 days followed by ALA for 4 hours led to large, tumor-selective increases in PpIX levels, and enhanced cell death upon illumination. Several mechanisms were identified that might explain the relatively improved therapeutic response. First, the expression of key enzymes in the heme synthesis pathway was altered, including upregulated coproporphyrinogen oxidase and downregulated ferrochelatase. Second, a 3- to 6-fold induction of p53 in 5-FU-pretreated tumors was noted. The fact that A431 contains a mutant form p53 did not prevent the development of a neoadjuvantal 5-FU effect. Furthermore, 5-FU pretreatment of 4T1 tumors (cells that completely lack p53), still led to significant beneficial inductions, that is, 2.5-fold for both PpIX and PDT-induced cell death. Thus, neoadjuvantal 5-FU combined with PDT represents a new therapeutic approach that appears useful even for p53-mutant and p53-null tumors.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.