DNA decoy drug, first of its kind, trialled in resistant melanoma

A drug that mimics broken strands of DNA and pushes treatment-resistant cancer cells to autodestruct has produced encouraging results in a first clinical trial.

The medicine, DT01, is the forerunner for a new class of drug developed by researchers at the Institut Curie in Paris, France. Rather than targeting a particular protein, enzyme or gene, these 'Dbait' drugs act as decoys within cancer cells, scrambling the internal signals which would otherwise enable the cells to repair themselves.

Designed to enhance the efficiency of conventional radiotherapy, DT01 appears safe and well-tolerated in patients with recurrent melanoma (an aggressive form of skin cancer) in a small dose-finding trial. The initial results suggest that DT01 acts specifically on tumours and does not increase the sensitivity of the rest of the skin to radiation.

DNA Therapeutics, the spin-out company now developing the Dbait drugs, further confirmed that 'responses have already been observed in the tumours treated by DT01 and radiotherapy, while no response [was observed] in the tumours treated by radiotherapy alone'.

Speaking to AFP, study leader Dr Christophe le Tourneau of the Institut Curie emphasised that the trial is a 'very, very early' one. Nonetheless, the results are likely to generate an upsurge in interest from biotech investors in DNA Therapeutics' unorthodox technology.

Dbait drugs would be administered to patients prior to a course of radio- or chemotherapy and are taken up by cancer cells in large quantities. The drugs' structure mimics a break in both DNA strands and is recognised by the cell's repair system as such. The result, a promotional video from DNA Therapeutics explains, 'is a fog of incoherent signals within the cell'.

'Acting like forgers, Dbait molecules make cancer cells treated with radiotherapy believe that they are far more severely damaged than they are', furthers Dr Marie Dutreix, who devised the Dbait concept and co-founded DNA Therapeutics. 'Accordingly, the tumour cells autodestruct'.

Should early tests of DT01 prove successful, the drug will progress to the next round of clinical trials designed to evaluate the efficiency of the treatment. DNA Technologies also hopes to start testing the drug in brain and liver cancer in combination with radio- or chemotherapy in 2013.