Scientists from the Paterson Institute for Cancer Research at Manchester University in the UK are planning to move a novel anticancer into a Phase I trial in children after it showed encouraging preclinical activity against cells from several types of childhood cancers.

Researchers from the Paterson Institute and the Royal Manchester Children’s Hospital found in laboratory tests that the drug, RH1, could destroy cancer cells from neuroblastoma, osteosarcoma and Ewing’s sarcoma, three types of childhood and adolescent cancer that are often resistant to currently available chemotherapies. The preclinical study revealed that even very low doses of RH1 could boost cancer cell death by around 50% compared with untreated cells.

The activity of RH1, described by the Paterson Institute as a “novel, bioreductively activated alkylating agent”, is greatly enhanced by the enzyme DT-diaphorase (DTD), which is found more extensively in adult tumours including lung, liver and breast cancer, the researchers noted. The drug recently completed a Phase I clinical trial in adults.

The planned study in children would be the first for a paediatric indication conducted through the drug development office of Cancer Research UK, which provides core funding for the Paterson Institute.

'Very potent'

The preclinical results were presented at the National Cancer Research Institute Conference in Birmingham. Dr Guy Makin, the lead researcher from the Paterson Institute, commented: “RH1 is a very potent agent and our pre-clinical results suggest that it could be effective against childhood tumours that express DTD. We hope that this will be just the first of many new agents that we can show are useful for treating childhood cancer.”

RH1 was synthesised from MeDZQ, an anti-tumour chemical that selectively kills cancer cells. The compound was manufactured as a water-soluble version of MeDZQ to enhance its clinical potential.

Some 1,500 new cases of childhood cancer are diagnosed in the UK each year. With advances in treating infectious diseases, cancer is now the most common cause of death from illness in children aged one to 15 years. Survival rates are actually high, at around 75%, but in many cases patients become resistant to drug treatment and need new options.