MADRID, 23 Jun. (EUROPA PRESS) –
A new precision medicine targeting cancer’s ability to repair its DNA has shown promising results in the first clinical trial of this class of drug, according to the authors in the Journal of Clinical Oncology.
The new study, designed to evaluate the safety of the drug, found that half of the patients who received the new drug alone or with platinum chemotherapy saw their cancer stop growing, and two patients saw their tumors shrink or disappear due to full.
Damage to DNA in cells is the main cause of cancer, but it is also a fundamental weakness in tumors, and cancer cells can be destroyed by further damaging your DNA or attacking its ability to repair it.
The new phase I trial tested the first of a new family of drugs that blocks a key DNA repair protein called ATR. Phase I trials are designed to assess the safety of new treatments, and it is unusual to see a clinical response at this stage.
A team from the London Cancer Research Institute and The Royal Marsden NHS Foundation Trust conducted a trial on the benefit of an ATR inhibitor called berzosertib, either alone or with chemotherapy in 40 patients with highly advanced tumors, treated in hospitals around the world. the world.
The researchers established the doses at which the drug was safe for use in additional clinical trials, and found that berzosertib alone caused only mild side effects.
Surprisingly for a phase I trial, funded by Merck, the drug’s manufacturer, the researchers also found that berzosertib stopped tumor growth in more than half of the patients who received the drug alone or with chemotherapy, 20 of 38 patients. whose response to treatment could be measured.
The drug’s benefit in blocking DNA repair was even more pronounced in patients who also received chemotherapy, which works by causing DNA damage. In these patients, 15 of 21, or 71 percent, saw their disease stabilize, suggesting that chemotherapy increased sensitivity to berzosertib.
A patient with advanced bowel cancer whose tumor contained failures in key DNA repair genes, including CHEK1 and ARID1A, responded remarkably well to berzosertib on its own, seeing its tumors disappear and remaining cancer-free for more than two years.
Another woman with advanced ovarian cancer whose disease had come back after treatment with a drug that blocks PARP, another key DNA repair protein, received the combination treatment and saw her tumors shrink.
The response of these patients suggests that berzosertib could be explored as a strategy to overcome resistance to the PARP family of inhibitors of targeted treatments.
The drug is now moving forward in additional trials, and the hope is that it can be developed into a new, targeted treatment for patients, and help overcome resistance to other precision drugs such as PARP inhibitors that target DNA repair.
Drug resistance, as cancers evolve in response to treatment, is one of the biggest challenges facing cancer research and treatment today.
The Cancer Research Institute (ICR), a research and charity institute, will focus on how to overcome cancer progression and drug resistance at its new Center for the Discovery of Cancer Drugs, for which it still needs raise the last £ 2m (€ 2.21m).
ICR discovered how to genetically target the first approved precision drug that attacks cancer’s ability to repair DNA, the PARP inhibitor, olaparib.
Professor Johann de Bono, Head of Drug Development at the Cancer Research Institute, London, and The Royal Marsden NHS Foundation Trust, notes that his clinical trial “is the first to assess the safety of a new family of cancer drugs targeted at people, and it’s encouraging to see some clinical responses even at this early stage. Now, we and others are planning more clinical trials of berzosertib and other drugs that block the ATR protein, “he adds.
“In the future, this new class of ATR inhibitor drugs could enhance the effect of treatments such as chemotherapy that target cancer DNA, expand our range of treatment options, and outperform resistance to other specific treatments,” he continues.
For his part, Professor Paul Workman, executive director of the Cancer Research Institute, London, adds that “targeting a cancer’s ability to repair its DNA is a fundamentally important avenue of cancer research that has provided some of the most important advances against the disease in recent years. “
“It is exciting to see that the first clinical trial of a drug targeting a key player in the DNA repair process has such promising results, and I look forward to the results of more studies that prove the benefit of this new family of targeted treatments.” concludes.
“I am eager to explore the potential of these ATR inhibitors to overcome resistance to other specific drugs and form effective treatment combinations. That is exactly the type of approach we will take at our new Cancer Drug Discovery Center as we search block out the cancer’s escape routes by creating a new generation of anti-evolution treatments. “
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