Basal-cell carcinoma targeted by new deoxyribozyme drug

A new class of drugs targeting the genetic material of skin cancer has been successfully tested in humans for the first time. This opens the way to new treatments for a range of conditions from skin cancers to eye diseases.

The drug Dz13 is a targeted molecular therapy that targets JUN messenger RNA, which is a product of the nuclear transcription factor c-Jun. Basal-cell carcinoma preferentially expresses c-Jun. A recent study involving nine patients was the first report of the use of a drug of this type in humans. The findings were published in The Lancet (2013; doi: 10.1016/S0140-6736(12)62166-7).

"Even though we were only testing for safety, there were unexpected positive effects," said Levon Khachigian, PhD, of the University of New South Wales, Australia, where the therapy was developed. "The drug knocked down levels of this bad protein and the tumors shrunk in the majority of patients."

The researchers hope subsequent trials will prove that larger doses of the drug over a longer time period will be more effective.

"Targeted molecular therapy like this might also offer novel, effective, and less invasive therapeutic options for basal-cell carcinoma," said coauthor Gary Halliday, PhD, of the University of Sydney in Australia.

Among the nine patients tested, all experienced reduced c-Jun expression compared with baseline, and five of the nine (56%) had decreased histological tumor depth. The treatment stimulated infiltration by inflammatory and immune cells. Single intratumoral injections of the treatment were safe and well tolerated at all three doses tested.

If the next stages of the clinical trials in basal-cell carcinoma are successful, the researchers hope that within 3 years, the drug could be used as a treatment for these cancers, reducing scarring and the costs and inconvenience associated with surgery.

Basal-cell carcinoma is the most common cancer among fair-skinned people worldwide with Australia having the highest incidence.

"This may be a 'one-size fits all' therapy, because it targets a master regulator gene called c-Jun which appears to be involved in a range of diseases," said Khachigian, who predicts that melanoma and eye diseases including macular degeneration and diabetic retinopathy will be likely future targets for research.

A phase one trial in skin melanoma is expected to begin in a month.
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