The research also found that the drug, called BMN 673, can work at a fraction of the concentration of some other drugs that work in a similar way.
That means that the effective dose in patients could be much lower, potentially reducing the likelihood of side-effects.
BMN 673, which is being researched at The Institute of Cancer Research (ICR), is from a family of molecules called PARP inhibitors. They target PARP proteins, which help repair wear and tear to DNA. In early human trials, these molecules have shown particular promise in fighting cancers such as breast and ovarian cancer in patients with mutations to the BRCA1 and BRCA2 genes.
The research was funded by Breakthrough Breast Cancer and the American Association for Cancer Research, and is published in the journal Clinical Cancer Research.
It was led by Dr Chris Lord and the ICR’s Chief Executive Professor Alan Ashworth working in combination with a drug company, Biomarin. Professor Ashworth was a key member of the team that discovered the BRCA2 gene in 1995, and he and Dr Lord have pioneered the use of PARP inhibitors in tackling cancer.
Early results from a first-in-human phase I clinical trial of BMN673, led by ICR researchers at The Royal Marsden NHS Foundation Trust, were announced in June. Those results showed that BMN673 was well tolerated by patients and showed excellent anti-tumour activity, particularly in patients with BRCA mutations.
The new study was designed to look in detail at the potency of BMN673, as well as its ability to selectively target cancer cells. The researchers also measured the effect of the drug when combined with other cancer drugs.
The results showed that BMN673 targeted tumour cells with BRCA1 or BRCA2 defects with 20- to more than 200-fold greater potency than existing PARP1/2 inhibitors. Results were similar in cells carrying cancer-causing mutations to a third gene, called PTEN. Effects were more pronounced when combined with other chemical agents including platinum drugs.
In mice, tumours with defects in DNA repair due to BRCA mutations or PTEN deficiency were profoundly sensitive to oral BMN 673 treatment, at well-tolerated doses. Some tumours disappeared completely after 28 days of treatment.
Dr Chris Lord, Senior Staff Scientist at the ICR, said: “Our study confirms BMN 673 as one of the most powerful molecules of its type and adds to the growing armoury of new anti-cancer agents.”
“This type of study plays an essential role in shaping later-stage research, including clinical trials. Our research shows that clinical trials of BMN673 have a good chance of success, and the effective dose needed to have an effect in patients should be relatively low.”