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The DNA of a woman whose lethal thyroid cancer unexpectedly “melted away” for 18 months has revealed new mechanisms of cancer response and resistance to the drug everolimus, said researchers from Dana-Farber Cancer Institute and the Broad Institute of MIT and Harvard.
The investigators discovered two previously unknown mutations in the cancer’s DNA. One made the woman’s cancer extraordinarily sensitive to everolimus, accounting for the remarkably long-lasting response. The second mutation was found in the DNA of her tumor after it had evolved resistance to the drug 18 months after treatment started, according to the study published in the October 9 issue of the New England Journal of Medicine.
The single case study illustrates how repeatedly sequencing a patient’s cancer DNA – first prior to treatment and again when the tumor shows signs of resistance – can identify unsuspected “response” and “resistance” mutations that may help guide treatment of other patients.
“This is personalized, precision medicine at its best,” said Jochen Lorch, MD, a thyroid cancer specialist at the Head and Neck Treatment Center at Dana-Farber and senior author of the report.
Having identified the mutation – in a gene called TSC2 – that caused the patient’s dramatic response to everolimus, researchers at Dana-Farber have opened a clinical trial to test the drug’s effectiveness in other patients with TSC2 mutations. This type of trial, sometimes called a “basket” trial, is becoming more common as studies of patients who are “exceptional responders” are revealing previously unknown response mutations to a variety of drugs. A basket trial pools patients with a particular response mutation, regardless of the type of cancer they have.
Posted on October 08, 2014
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