More than half the mutations that cause oesophageal adenocarcinoma could be targeted by drugs currently in trials for other cancer types, according to research published in Nature Genetics last night.
For the first time, scientists have mapped the mutations in unprecedented detail.
This could help to develop personalised treatments for oesophageal cancer patients, providing options that are not yet available to patients beyond standard chemotherapy, radiotherapy or surgery, the researchers say.
Cancer Research UK researchers at the University of Cambridge, England, used whole genome sequencing and whole exome sequencing to map mutations in OAC, the main subtype of oesophageal cancer in England.
They found driver mutations for OAC in 99% of patients and more than 50% were sensitive to drugs (CDK4/6 inhibitors) already in clinical trials for breast cancer. This means phase II/III clinical trials to treat oesophageal cancer could be feasible in one to two years.
Women were found to have more KRAS mutations, which are rarely seen in oesophageal cancer, than men, which the research team says could indicate a different sub-type of the disease in women.
Professor Rebecca Fitzgerald, Cancer Research UK funded scientist and lead researcher at the MRC Cancer Unit, said: “This research could completely shift the paradigm from giving oesophageal cancer patients the same chemotherapy that we know doesn’t always work, to more targeted treatments based on individual characteristics of a patient’s cancer.
“We are now designing clinical trials that provide real-time analysis of patients’ genes to offer patients the best treatment based on their own genome.
“This research could also provide better options for older patients, who are more likely to develop oesophageal cancer, and who are often not fit enough for current treatment options.”
Professor Karen Vousden, Cancer Research UK’s chief scientist, said: “Understanding which mutations are causing the disease could lead to targeted treatments and earlier detection. This is something that would never have been possible without huge advances in technology.”
Nature Genetics 4 February 2019
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