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Cited by 390Nonmelanoma Skin Cancer StudiesSkin Protection and AgingDNA Repair Mechanisms

Effect of topically applied T4 endonuclease V in liposomes on skin cancer in xeroderma pigmentosum: a randomised study

Yarosh, Daniel, Klein, Jonathan, O'Connor, Adrienne, Hawk, John, Rafal, Elyse, Wolf, Peter·2001·The Lancet
DOI 10.1016/s0140-6736(00)04214-8
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Abstract

Background In patients with xeroderma pigmentosum the frequency of all forms of skin cancer is higher than in the general population, owing to a genetic defect in DNA repair. The bacterial DNA repair enzyme, T4 endonuclease V, delivered intracellularly, increases the rate of repair of sunlight-induced DNA damage in human cells. We tested the ability of this enzyme in a liposomal delivery vehicle applied topically (T4N5 liposome lotion) to lower the rate of new skin cancers in patients with xeroderma pigmentosum.Methods 30 patients were enrolled in this prospective, multicentre, double-blind study. Patients were randomly assigned T4N5 liposome lotion or a placebo liposome lotion, to be applied daily for 1 year. At 3-monthly visits, new actinic keratoses and basal-cell carcinomas were identified and removed. Analyses were by intention to treat.Findings 20 patients were assigned T4N5 liposome lotion and ten placebo lotion; one placebo-group patient withdrew before treatment and one withdrew with progressive disease at 9 months. The annualised rate of new actinic keratoses was 8.2 among the patients assigned T4N5 liposome lotion and 25.9 among those assigned placebo (difference 17.7 [95% CI 11.8-26.5]; p=0.004 by Poisson modelling). For basal-cell carcinoma, the annualised rates of new lesions were 3.8 in the treatment group and 5.4 in the placebo group (difference 1.6 [0.38-2.82]). No significant adverse effects were found among any of the patients.Interpretation DNA damage has an important role in the development of skin cancer and precancerous skin lesions. The topical application of DNA repair enzymes to sun-damaged skin of patients with xeroderma pigmentosum lowered the rate of development of two forms of these lesions during a year of treatment.

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  • Clinical trials using a topically applied liposomal formulation with bacteriophage T4 CPD damage removal enzyme T4 endonuclease V resulted in lowered actinic keratoses and basal-cell carcinoma incidence in XP patients.

    “Clinical trials with the use of topically applied liposomal formulation with bacteriophage T4 CPD damage removal enzyme – T4 endonuclease V resulted in lowered actinic keratoses and basal-cell carcinoma incidence in XP-patients [181,182].”

    From Focus on UV-Induced DNA Damage and Repair—Disease Relevance and Protective Strategies (2020) · cites this paper as [181]

  • In clinical trials with XP patients using topically delivered T4-pdg, new pre-cancerous lesions (actinic keratosis) were reduced by 68% and new cases of BCC were reduced by 30% compared to placebo lotion.

    “Results of clinical trials with XP patients using topically delivered T4-pdg showed that new pre-cancerous lesions (actinic keratosis) were reduced by 68% and new cases of BCC were reduced by 30% compared to patients treated with placebo lotion17.”

    From Modulation of UVB-induced Carcinogenesis by Activation of Alternative DNA Repair Pathways (2018) · cites this paper as [17]

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Authors
Yarosh, D., Klein, J., O'Connor, A., Hawk, J., Rafal, E., & Wolf, P.
Affiliations
  • St Thomas' Hospital (GB)
  • Cornell University (US)
  • University of Graz (AT)
Corresponding author
Yarosh, Daniel
ORCID
Venue
The Lancet
Publisher
Elsevier BV
Published
2001-03
Volume
357
Issue
9260
Pages
926-929
ISSN
  • 0099-5355 (ISSN-L)
  • 0140-6736
DOI
10.1016/s0140-6736(00)04214-8
OpenAlex
W2124110334
Cited by
390
References
21
Citations by year
2026: 4 · 2025: 5 · 2024: 3 · 2023: 10 · 2022: 6 · 2021: 8 · 2020: 12 · 2019: 7 · 2018: 15 · 2017: 17 · 2016: 22 · 2015: 13 · 2014: 16 · 2013: 5 · 2012: 12
FWCI
18.06
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • The Lancet (publishedVersion)
  • PubMed (publishedVersion)
  • Research Portal (King's College London) (submittedVersion)
Funders
U.S. Food and Drug Administration (FD-R-001505)
Topics
  • Health Sciences › Medicine › Epidemiology › Nonmelanoma Skin Cancer Studies
  • Health Sciences › Medicine › Dermatology › Skin Protection and Aging
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
Keywords
xeroderma pigmentosum, T4 endonuclease V, liposomal drug delivery, skin cancer prevention, actinic keratosis, basal cell carcinoma, DNA repair deficiency, sun damage, precancerous skin lesions
MeSH terms
Administration, Topical, Adolescent, Adult, Carcinoma, Basal Cell, Basal Cell Carcinoma, Child, Child, Preschool, DNA Repair, Double-Blind Method, Endodeoxyribonucleases, Europe, Female, Humans, Keratosis, Liposomes, Male, Middle Aged, Photosensitivity Disorders, Prospective Studies, Regression Analysis, Skin Neoplasms, United States, Viral Proteins, Xeroderma Pigmentosum, Multivariate Analysis, Deoxyribonuclease (Pyrimidine Dimer)

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