Researchers at Dublin City University (DCU) have discovered a new way to prepare DNA-damaging drug molecules. The long-term goal of this work is providing new effective, personalised cancer treatments with lower side effects.

The discovery was made by DCU’s Dr Andrew Kellett and his team of researchers who collaborated with scientists from Sweden’s Chalmers University of Technology.

They developed a ‘click and cut’ method to address the challenge presented by the increasing patient resistance to metal-based drugs, which are often used to treat many forms of cancer.

The method involves attaching metal ion binding groups to a central scaffold using ‘click chemistry’. With this approach, the team prepared a library of drug candidates and identified a lead agent that had high potential for treating cancer.

This library was screened together with different types of metal ions. One compound was identified that could bind strongly with copper ions and produce a unique type of DNA damage that is not possible with existing metal-based drugs.

The compound was then identified to produce DNA damage within primary human cells, and imaging was performed to visualise the amount of damage and the type of DNA repair enzymes activated in response.

Researchers said the results were encouraging and showed the compound could produce a high amount of specific damage.

“These results are promising and indicate a new avenue for preparing unique types of drug molecules,” Kellet said. “Although click chemistry has an extensive range of applications — particularly in the field of nucleic acid chemistry — it has not yet been widely considered as a way to construct DNA-damaging metallodrugs.”

New therapies for difficult-to-treat cancers such as triple-negative breast cancer or glioblastoma multiforme are highly sought after due to the lack of treatments currently available.

The research team now aims to expand the new method and develop more therapies targeted at specific cancer-causing genes. The work has been published in Nucleic Acids Research.

Blathnaid O’Dea

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