British cancer researchers believe they might be able to ensure a “promising” new stomach cancer drug class is used in a way that outsmarts the disease’s ability to develop resistance.
The project at the Institute of Cancer Research, London, centres on ATR inhibitors. The research has pinpointed two genes that the cancer can switch off in order to become resistant to the drugs.
ATR inhibitors block a protein which helps cancer cells repair DNA and supports successful cell division.
Using CRISPR technology, the researchers found that if two genes SMG8 and SMG9 were switched off, the ATR inhibitors would cease to be effective. They report their findings today in *Cancer Research*.
They now want to develop tests to identify patients in whom this might happen. They also hold out the prospect of additional drugs to disable the cancer’s ability to switch off these genes.
About 25% of patients with stomach cancer may benefit from ATR inhibitors, which have shown promise in early trials – which have also highlighted the risk of drug resistance.
Researcher Professor Chris Lord said: “ATR inhibitor drugs represent a promising and badly needed new treatment option for people with stomach cancer – so it is important to understand how resistance can emerge. We believe our findings could lead to new tests and ultimately treatment strategies, to allow us to stay one step ahead of cancer.
“Our discovery suggests three key genes are involved in making stomach cancers resistant to treatment with ATR inhibitors. It could lay the groundwork for future clinical trials to test out new drug combinations and other treatment approaches designed to overcome cancer’s drug resistance.”
Dr Irene Chong, a fellow researcher and a clinical oncologist at the Royal Marsden Hospital, said: “Our study shows that ATR inhibitors may represent an important therapeutic option for subgroups of patients with gastric cancer, and our work identified a novel mechanism of resistance, which could help us understand how we are able to overcome drug resistance. This could ultimately lead to new treatment strategies in the future.”
*Cancer Research* 24 October 2022
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