The drug that targets a cancer cells’ ability to repair its DNA, has shown early signs of working in its first patent trial.
A team at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust, have discovered a treatment that stopped tumours growing in over half of its participants.
The method, using berzosertib either on its own or with chemotherapy in 40 patients with very advanced tumours, showed encouraging signs in 20 of the 38 patients whose response could be measured.
The trial found that half of patients given the new drug either alone or with platinum chemotherapy saw their cancer stopped growing, and two patients saw their tumours shrink or disappear completely.
The phase I trial tested berzosertib, which belongs to a new class of drugs known as ATR inhibitors. These type of drugs work by blocking the function of a protein called ATR, which helps cancer cells fix DNA.
Phase I trials are designed to assess the safety of new treatments, and the scientists say it’s unusual to see a clinical response at this stage.
Professor Johann de Bono, Head of Drug Development at the ICR and The Royal Marsden, 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. Now, we and others are planning further clinical trials of berzosertib and other drugs blocking the ATR protein.
“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.”
The drug’s benefit in blocking DNA repair was even more marked in patients also given chemotherapy, which works by causing DNA damage.
In these patients, 15 of 21, or 71 per cent, saw their disease stabilise, suggesting that chemotherapy boosted sensitivity to berzosertib.
One patient with advanced bowel cancer responded remarkably well to berzosertib on its own, seeing his tumours disappear and staying cancer free for more than two years.
Another woman with advanced ovarian cancer whose disease had come back after treatment, received the combination treatment and saw her tumours shrink.
Drug resistance is one of the biggest challenges facing cancer research and treatment.
Professor Paul Workman, Chief Executive of The Institute of Cancer Research, London, said: “Targeting a cancer’s ability to repair its DNA is a fundamentally important avenue of cancer research which has delivered some of the most important advances against the disease in recent years.
“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.
“I’m keen to explore the potential for these ATR inhibitors to overcome resistance to other targeted drugs and to form effective treatment combinations. That’s exactly the kind of approach we will be taking in our new Centre for Cancer Drug Discovery as we look to block off cancer’s escape routes by creating a new generation of anti-evolution treatments.”
The drug is now moving forward in further trials and the researchers hope that it can be developed into a new targeted treatment for patients and to overcome resistance from other medicines.
On this day…
In 1922… John Postgate was born. Described as a “father figure of British microbiology”, his findings contributed to the production of industrially important sulphuric acid, and to converting atmospheric nitrogen into fertiliser for plants.
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