DNA repair enzymes to fight cancer

The body has a set of DNA repair enzymes that clean up damage to the genome, to reduce potential problems. Many commonly used cancer chemotherapies work by alkylating DNA. However, the DNA repair enzymes are just as capable of repairing this alkylation as if it were damage from any other source, and so they act to overcome the effects of the therapy, reducing its effectiveness.

One such enzyme that repairs alkylation damage to DNA is known as AlkB. Researchers at the University of Oxford have carried out mechanistic studies on this enzyme, and have demonstrated that the enzyme can be inhibited by substrate analogues.

Inhibitors of this enzyme could potentially allow a useful reduction in the amount of cytotoxic alkylating agents used in cancer chemotherapy, by suppressing the repair response that reduces the effectiveness of the therapy.

For instance, a similar combination therapy approach is already very successfully used in the field of antibiotics. In one example from this field, amoxycillin is used in combination with clavulanic acid; the clavulanic acid inhibits an enzyme responsible for bacterial resistance to the antibiotic.

Cytotoxic therapies are used for the majority of advanced stage cancer cases and in 2001 the market size for alkylating agent therapies was $417 million in the US alone. In 2000 there were 10 million new cases and 6.2 million cancer-related deaths world-wide, so there is enormous scope for any methodology that could increase the effectiveness of these therapies.

This method is patent application protected. Isis would be happy to talk to companies interested in developing the commercial opportunities for this technology.