An experimental cancer drug which targets cancer cells’ DNA repair could be an effective treatment for a range of cancers, the first clinical trial in patients has shown.
The drug has shown particular potential in cancers which have mutations to one or both of the BRCA genes.
Researchers at The Institute of Cancer Research, London, led a worldwide multicentre clinical trial for the targeted treatment talazoparib in 71 patients with cancers of different types.
The results show that talazoparib could benefit patients in the clinic – particularly women with BRCA-mutated breast and ovarian cancer.
Published in the journal Cancer Discovery, the phase I trial was supported by a range of funders including Cancer Research UK,and the National Institute for Health Research Biomedical Research Centre at the ICR and The Royal Marsden NHS Foundation Trust.
The Drug Development Unit aims to integrate preclinical drug discovery, proof-of-principle phase I trials and tumour-specific evaluation of novel agents.
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Genetic errors
Some cancer cells become overly reliant on a protein called PARP, which repairs broken DNA, because genetic errors make other DNA repair systems – including the BRCA system – defective.
PARP inhibitors, like talazoparib, kill BRCA-mutated cancer cells by taking advantage of their reliance on PARP.
In the study, the researchers found that the drug was well tolerated and caused tumour shrinkage or slower growth in some patients – particularly those with mutations to one or both of the BRCA genes.
Five months after beginning the trial, seven of 14 women with BRCA-mutated breast cancer, and five of 12 with BRCA-mutated ovarian cancer, had confirmed clinical benefit from the drug. So did some patients with BRCA-mutated pancreatic and lung cancer.
Lead study author Professor Johann de Bono, Regius Professor of Cancer Research at the ICR and Clinical Consultant at The Royal Marsden, said: “Talazoparib is an exciting new PARP inhibitor, which displays more potency in the lab than other drugs currently approved for use. Our trial is the first of the drug and confirms there is a benefit for some patients with BRCA mutated cancers, as well as its safety.”