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DNAzyme targeting c-jun suppresses skin cancer growth

Hong Cai1, Fernando S Santiago, Leonel Prado-Lourenco

  • 1Centre for Vascular Research, University of New South Wales, Sydney, New South Wales 2052, Australia.

Science Translational Medicine
|June 23, 2012
PubMed

Insights

A novel DNAzyme, Dz13, effectively inhibits growth of basal cell and squamous cell skin cancers by targeting c-jun mRNA. Toxicology studies indicate Dz13 is safe, suggesting potential as a new human skin cancer therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Skin cancer incidence is rising globally, necessitating novel therapeutic strategies.
  • Basal cell carcinoma and squamous cell carcinoma are the most common types of skin cancer.
  • Targeting key oncogenic pathways, such as c-jun mRNA, presents a potential therapeutic avenue.

Purpose of the Study:

  • To evaluate the efficacy of a DNAzyme, Dz13, targeting c-jun mRNA in inhibiting the growth of established basal cell and squamous cell carcinomas.
  • To assess the safety and tolerability of Dz13 through comprehensive toxicology studies.
  • To investigate the mechanisms underlying Dz13's anti-tumor effects, including effects on metastasis, neovascularization, apoptosis, and tumor immunity.

Main Methods:

  • Dz13 was administered to mice with established basal cell and squamous cell carcinomas.
  • Tumor growth, metastasis (lung nodule formation), neovascularization, and apoptosis were assessed.
  • Mechanisms of action, including tumor immunity induction, were investigated.
  • Good laboratory practice-compliant toxicology studies were conducted in non-human primates and rodents.
  • In vitro bioassays were performed to assess off-target effects.

Main Results:

  • Dz13 significantly inhibited tumor growth in both immunodeficient and immunocompetent mice.
  • Dz13 reduced lung metastasis and suppressed tumor neovascularization in mice and zebrafish.
  • Increased apoptosis of tumor cells and induction of tumor immunity were observed.
  • Toxicology studies demonstrated Dz13 to be safe and well tolerated across species.
  • Dz13 showed minimal interference in over 70 in vitro bioassays, indicating low off-target potential.

Conclusions:

  • Dz13 demonstrates significant therapeutic potential for treating basal cell and squamous cell skin cancers.
  • The DNAzyme's efficacy is partly mediated by inducing anti-tumor immunity.
  • Dz13 exhibits a favorable safety profile and low propensity for off-target effects, supporting its advancement to clinical trials.

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