Mutations of the KRAS gene has a role in 90 percent of pancreatic, 45 percent of bowel and 40 percent of lung cancers. They cause changes to a key protein – dubbed the death star for its spherical appearance and impenetrable, drug-resistant surface – which trigger excessive cell growth.
The gene can have many different mutations but medicines have so far only succeeded in targeting one.
Now a powerful combination of two drugs is thought to halt cancer growth caused by multiple deadly variants, potentially benefiting thousands.
Dr Anna Minchom, of The Royal Marsden and The Institute of Cancer Research in London, said: “It’s great to see that this innovative drug combination is showing potential for treating patients with a range of cancers.
Patients with KRAS-mutated nonsmall cell lung cancer, apart from those with a subtype known as KRAS G12C, do not currently have targeted treatment options.”
She said it was “promising” that patients had no severe side effects.
The NHS said in March the drug sotorasib would be given to up to 600 patients with non-small cell lung cancer and the KRAS G12C mutation.
However, previous trials of therapies intended to tackle multiple variants failed due to severe side effects.
The latest study was of 30 patients whose other treatments had failed.
Two drugs – VS-6766 and everolimus – were given twice weekly for three weeks, followed by a week off to limit toxic side effects.
They work by blocking two biological pathways KRAS relies on to fuel cancer growth. Among 11 with highly advanced non-small cell lung cancer half saw their cancer’s growth halted for at least six months, double the time expected for chemotherapy.
Other patients with ovarian and thyroid cancers also responded well.
Professor Udai Banerji, at the ICR, said it “could represent a new treatment paradigm for KRAS mutations across multiple tumour types”.
The findings were presented to the American Society of Clinical Oncology annual meeting in Chicago.
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