DNA damage is the fundamental cause of cancer – leading to mutations in key genes that allow cancer cells to divide uncontrollably. But it can also be a key weakness of tumors that can be exploited, since cancer cells can be killed by further damaging their DNA or stopping them from repairing it.
A new drug, BAY1895344, which stops cancer from repairing its DNA so it can continue to grow and proliferate, has shown promise in an early clinical trial.
BAY1895344 belongs to a new class of drugs known as ATR inhibitors. ATR is a key molecule involved in repairing DNA damages. By blocking it, cancer cells can no longer repair DNA damages and die.
The drug was tested in humans for the first time. It was well tolerated and stopped the growth of tumors in over half of patients treated. It is orally administered.
About the Trial
This was a phase I trial. People in the trial had a range of advanced, heavily pre-treated cancers including breast, bowel and prostate cancers. These patients were very sick.
The trial involved 21 patients.
The aim of the trial was to evaluate the safety of the ATR inhibitor BAY1895344 and to identify the maximum tolerated dose that could be safely given to a group of cancer patients who had already previously been treated with multiple other drugs.
The researchers found that the drug was well tolerated by patients – and better still, that there were encouraging signs that it was effective against advanced cancers with defects in the ATR gene.
BAY1895344 stopped tumor growth in eight out of the 21 patients and shrunk the tumors of another four patients with ATM mutations – which is remarkably positive for a phase I trial with a new drug.
The effectiveness of the drug seemed to be long lasting, with an average period of response of 316 days!
Three out of four patients who had their tumors shrunk remained on treatment for more than a year.
The most common side effect reported was anaemia, which was managed with the help of blood transfusions and did not usually require the treatment to be stopped.
The Potential of ATR Inhibitors
Recently, another phase I trial also showed benefits for an ATR inhibitor, called Berzosertib, in patients with very advanced tumors, either on its own or with chemotherapy.
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