A drug that may one day be used to treat skin cancer has been found to be safe for use on humans and may reduce the size of a tumour, according to the first ever human trials of the drug.
The drug, called Dz13, works by switching off a gene called c-Jun that is linked to the production of a protein that causes cancer to grow and spread.
It may one day be used to treat other cancers, the researchers said.
Dz13 has been tested in mice but, until now, had not been tested on humans.
The study, published in the journal The Lancet involved injecting Dz13 into nine patients suffering Australia’s most common skin cancer, basal-cell carcinoma.
All patients completed the study with no drug-related serious adverse events.*
All nine patients were found to have lower levels of the target protein. For five of the patients, the researchers noted that the tumour had shrunk in size.
“This was a safety and tolerability study and we saw no [serious]* side effects or deleterious effects at all,” said Professor Gary Halliday from the Discipline of Dermatology at the University of Sydney, a co-author of the study.
“These trials showed it to be completely safe. There is a lot of scope to use this on other cancers and in fact we are about to embark on a trial of this drug on melanoma.”
Professor Halliday said the advantage of Dz13 was that it targets only the c-Jun gene, which scientists think is expressed in abnormal tissue, with little expression in normal tissue.
“A lot of other drugs used in cancer treatment have off-target effects, which is not absolutely desirable, whereas Dz13 is specific*,” he said.
Professor Halliday said tests on mice had shown Dz13 caused tumours to virtually disappear, but it was too soon to say if the same effect would be seen in humans.
“We have not done clinical efficacy trials yet but even if we found that it only reduced the volume of the tumour, the amount of surgery would be less. So you wouldn’t need to take out such a huge amount of skin,” he said.
“That’s advantageous, particularly on the face or near the eye or anywhere close to nerves or vital function, where we really want to take out minimal tissue.”
Professor Halliday said the drug could be available within three years.
Professor Levon Khachigian, Director of the UNSW Centre for Vascular Research and a co-author of the new study, said the human trial tested for safety but showed unexpected positive effects.
“The drug knocked down levels of c-Jun and the tumours shrunk in the majority of patients,” he said.
Professor Ian Olver, Clinical Professor of Oncology at the Cancer Council Australia (which helped to fund the research), said the researchers had shown the drug could work.
“I think it provides a third option for basal cell carcinoma in that usually they are treated by surgery, they are very responsive to radiotherapy, but for those too large or not appropriate for those two treatments or for ones that have relapsed after radiotherapy, this could be another option for treatment,” said Professor Olver.
Professor Rodney Sinclair, Director of Dermatology at Epworth Hospital at University of Melbourne, said the study showed proof of concept.
“It identifies a new molecular pathway that is involved in skin cancer development. Basal-cell skin cancers were shown to shrink but did not disappear,” said Professor Sinclair, who was not involved in the research.
“Until dose ranging studies identify a dose that reliably cures basal-cell carcinoma, surgery will remain the principal treatment for skin cancer.”
Professor Sinclair said that while there are an increasing number of non-surgical treatments for basal-cell carcinoma, their role is limited to the low risk, superficial form of the cancer.
“New non-surgical treatments for high risk nodular and morpheic basal-cell carcinoma are needed,” he said.
*Editor’s note and correction:
This article was corrected on January 11, 2016 to replace the sentence “After a single injection of the drug, there were no adverse effects in any of the patients treated with the drug” with “All patients completed the study with no drug-related serious adverse events.”
The word “serious” was also added in brackets to this quote from Professor Gary Halliday: “This was a safety and tolerability study and we saw no [serious] side effects or deleterious effects at all.”
The study this article reports on, published in The Lancet in 2013, found that:
Seven adverse events were reported in four patients. Of these, only transient (less than 24h) swelling at the injection site, discomfort, and nausea were possibly related to the study drug, and these three events were reported by the same patient, who received the 10 µg dose. The adverse events in the other three patients were deemed unrelated to Dz13.
All events were mild and self-limiting without treatment, except for a moderate wound infection with phlebitis after excision that required a course of antibiotics and an anti-inflammatory agent. No patient withdrew from the study because of adverse events.
A quote by Professor Halliday saying “Dz13 is completely specific” was changed to “Dz13 is specific.”