Precision cancer drug targets DNA repair

A new anti-tumour drug that prevents cancer cells from repairing their DNA shows promising results in an early-stage clinical trial.

The purpose of this drug, BAY1895344, is to inhibit the DNA repair mechanism of tumours by targeting a key molecule called ATR. The first-in-human clinical trial of BAY1895344 was conducted by a group of scientists from the Institute of Cancer Research (ICR) and the Royal Marsden NHS Foundation Trust to treat a variety of advanced, heavily pre-treated solid tumours. They showed that the oral administrated drug was well tolerated, without any significant side effects and stopped tumour growth in over half of patients tested.

'The new drug, which is currently known only by the code BAY1895344, works by blocking a molecule called ATR which is involved in repairing DNA.' said study leader Professor Johann de Bono, professor of experimental cancer medicine at the ICR and consultant medical oncologist at the Royal Marsden NHS Foundation Trust.

DNA damage is a major cause of cancer, which induces the uncontrollable replication of tumour cells. However, in order to survive, cancer cells have to trigger mechanisms to avoid further damage to their DNA. As such, drugs targeting cancer cells by further damaging their DNA or stopping them from being repaired, ultimately lead to the death of the cancer cell.

One surprising result was the efficacy of BAY1895344 in patients who already had mutations in genes implicated in the development of cancer (eg, ATM or BRCA1). 

'It seems to be especially effective in patients whose tumours have defects in a gene called ATM which mean their ability to repair DNA is already weakened – suggesting that this could become a new form of targeted treatment.' added Professor de Bono.

The scientists hope that BAY1895344 can be developed into a new targeted treatment for patients with a variety of cancers, such as breast, bowel and prostate, which already contain defects in certain DNA repair genes.

'It is exciting to see a new class of precision medicine showing such promise in early trials... I am hopeful that later-stage trials will show that this new class of ATR inhibitors can prove effective against cancers with defective systems for DNA repair, and we are keen to investigate whether they could prevent tumours from developing resistance to another important class of medicine called PARP inhibitors, which work in a similar way.' Professor Paul Workman, chief executive of the ICR, said.

These findings were recently published in the journal Cancer Discovery.