By Richard Saltus – Dana-Farber Cancer Institute.
Finding genetic causes of dramatic cancer drug responses could have broad benefits
When he decided to try a drug called everolimus for the first time in a rare, highly lethal type of thyroid cancer, oncologist Jochen Lorch, MD, had little hope it would help 57-year-old Grace Silva. “No therapies have ever worked for anaplastic thyroid cancer,” he said. In 2011, Silva had exhausted standard treatment and tumours had spread to her lungs.
What happened next some might call a miracle. “Much to our surprise, after about six months, her tumour had almost completely disappeared,” says Lorch. This response lasted for 18 months, until the cancer became resistant to everolimus, according to Lorch.
“I feel blessed,” says Silva, who continues to battle the disease in 2014. “I thought I would never have grandchildren — and now I have two!”
Researchers call such dramatic, unexpected outcomes “exceptional responses.” They typically involve experimental drugs that have failed in most similar cases but are extraordinarily effective in one or a few individuals. Until now, they have mystified physicians, cancer researchers and drug makers.
But very recently, in a handful of recent reports, researchers have begun solving these puzzles. The answers lie hidden in the genes and chromosomes of a patient’s cancer, which were found to contain rare, unsuspected DNA mutations that made the cancer cells highly sensitive to a particular drug.
These “response mutations” — some of them previously unknown to scientists — weren’t present in the tumours of most patients, explaining why they did not benefit from the same drug. Silva’s case and that of another patient who had an unusually long-lasting remission after drug treatment were reported in 2014 by scientists at Dana-Farber, Brigham and Women’s Hospital, and the Broad Institute of MIT and Harvard, along with collaborators at the Whitehead Institute for Biomedical Research.
These discoveries are opening new windows on what determines a tumour’s response — or lack of one — to cancer drugs. Studying exceptional responders could help cancer scientists identify other patients who may benefit from drugs that had been deemed failures — and increase the precision of personalized cancer care.
“Traditionally, the exceptional responses have been anecdotal case reports that may or may not ever be repeated, and you couldn’t learn a lot from them,” says Lorch. “But now we have the tools to find out why these patients responded so well,” he adds…read more.