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New drug stops cancer cells from repairing their DNA

29 June 2020
Appeared in BioNews 1053

A new drug targeting a cancer's ability to repair its DNA has shown favourable results in its first clinical trial.

The phase I trial was designed to test the drug's safety, yet results have shown that in half of the patients given the new drug, berzosertib, their cancer stopped growing, and in two patients their tumour shrunk or completely disappeared.

Lead author Professor Johann de Bono, head of drug development at the Institute of Cancer Research (ICR), London, and the Royal Marsden NHS Foundation Trust, London, said: 'Our new clinical trial is the first to test the safety of a brand new family of targeted cancer drugs in people, and it's encouraging to see some clinical responses even at this early stage.'

Berzosertib belongs to a new class of drugs known as ATR inhibitors, which work by blocking an important protein that helps cancer cells repair DNA damage. By blocking this protein, cancer cells can be killed by preventing them from being able to repair their DNA.

Scientists at the ICR and the Royal Marsden published the results of their clinical trial in the Journal of Clinical Oncology. In the phase I trial, the scientists gave berzosertib, either on its own or with chemotherapy, to 40 patients with very advanced tumours.

The dose at which the drug is safe for use in further clinical trials was established, and the scientists also discovered that berzosertib only caused mild side-effects. Surprisingly for a phase I trial, the scientists found the drug stopped tumours growing in over half of the patients who were given the drug, either on its own, or with chemotherapy.

Professor Paul Workman, chief executive of the ICR, said: 'Targeting a cancer's ability to repair its DNA is a fundamentally important avenue of cancer research... It's exciting to see the first clinical trial of a drug targeting a key player in the DNA repair process have such promising results, and I look forward to the results of further studies testing the benefit of this new family of targeted treatments.'

The drug's beneficial effect was even more clear in patients who also received chemotherapy, with 71 percent of patients seeing their cancer stabilise.

A patient with advanced bowel cancer was administered berzosertib on its own. His tumours disappeared and he has remained cancer-free for over two years.

A further patient with advanced ovarian cancer was administered berzosertib and chemotherapy. This combination therapy resulted in her tumours shrinking, even after her cancer had returned after becoming resistant to her original drug treatment.

Berzosertib is now moving forward in clinical development and it is hoped can be developed into a new targeted drug treatment for very advanced cancer patients.

Professor de Bono concluded: 'In future, this new class of ATR inhibiting drugs could boost the effect of treatments like chemotherapy that target cancer DNA, expand our range of treatment options and overcome resistance to other targeted treatments.'

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