Fundamentally, cancer was caused by damaging the DNA in cells. At the same time, this also turns out to be one of its weaknesses. As such, cancer cells can be theoretically destroyed by impairing their DNA or switching off its ability to repair it. Recently, a group of researchers at the Institute of Cancer Research (ICR) and The Royal Marsden NHS (National Health Service) Foundation Trust in UK uncovered a new class of precision medicine that will strip cancer cells’ abilities to repair their DNA. The promising result was obtained in the first clinical trial of a new family of drugs which blocks a key DNA repair protein known as ATR.
Blocking cancer cells’ key DNA repair protein
Initially, researchers dedicated this Phase 1 trial to test whether Berzosertib, an ATR inhibitor is safe to be used in new treatment. They knew that it’s unlikely to return with a clinical response at the moment. Yet, what the researchers found was half of the patients administered with the new drug, either alone or with platinum chemotherapy, saw their cancer stop growing. Two patients have got their tumors reduced in size or completely gone.
Specifically, researchers were surprised that tumors in 20 out of 38 patients, whose treatment response could be assessed, stopped growing. Benefit of Berzosertib is most obvious among patients who were also undergoing chemotherapy. 71% or 15 out of 21 of such patients had their cancer stabilized. Researchers believe this is probably due to chemotherapy lifting the sensitivity of the drug.
A patient with advanced bowel cancer responded especially well to Berzosertib, as it damages the key DNA repair genes including CHEK1 and ARID1A in his tumor cell. His tumor disappeared and he has been living cancer free for over two years. Another patient with advanced ovarian cancer, who was using another drug to block key DAN repair protein – PARP, suffered a relapse but her tumors became smaller with Berzosertib. This means Berzosertib may also be used to overcome the resistance to the PARP inhibitor family.
Moving onto the next level of clinical trial
All findings were published in the Journal of Clinical Oncology yesterday (22 June). Researchers are now moving Berzosertib onto the next level of clinical trial. They hope that it will eventually be developed into a new targeted treatment for patients and assist them in their combat against drug resistance.
Professor Paul Workman, ICR Chief Executive said ICR is keen to explore the potential for these ATR inhibitors to overcome resistance to other targeted drugs and to form effective treatment combinations. The approach is what the institute is looking for to block off cancer’s escape routes by creating a new generation of treatments to prevent cancer evolution.
Professor Johann de Bono, Head of Drug Development at ICR adds, “in the future, this new class of ATR inhibiting drug could boost the effect of treatment like chemotherapy that target cancer DNA, expand our range of treatment options and overcome resistance to other targeted treatments”.