An Unlikely Cure Signals

BIOLOGY MEDICINE An Unlikely Cure Signals New Hope for Cancer How “exceptionalresponders’ ‘arerevolutionizing treatment for the deadly desease BY KAT MCGOWAN UST LIKE EVERY NEW drug the oncologists at Memorial Sloan-Kettering Cancer Center test- ed against bladder cancer in the last 20 years, this one didn’t seem to be doing any good. For- ty-four people in the study were given everolimus in a last-ditch attempt to slow down or stop their advanced cancer. When the researchers analyzed the data, they could see that the drug wasn’t slowing or stopping tumor growth. Everolimus seemed to be another bust. Then there was patient number 45. She joined the trial with advanced metastatic cancer. Tumors had invaded deep into her abdomen, clouding her CT scan with solid grey blotches. She was 73 years old. None of the standard bladder cancer drugs were working for her anymore; she had “failed treatment,” in the dismal lingo of oncologists. She enrolled in the study only because she happened to be a patient at Sloan-Ketter- ingin January 2010. In April 2010, her cancer was gone. This sort of happy surprise is not unheard of in drug studies. Bodies are fluky, each with its own idiosyncratic combination of genetic blueprints and J environmental inputs. So sometimes a patient will be cured by a drug that is useless for everyone else. In the past, these spectacular reactions were written off as outlier responses that defied explanation—medical mysteries. Doctors just shrugged their shoulders and thanked their lucky stars that even though the study tanked, they did manage to help one person. But this time was different. Clinical oncologist David Solit, director of developmental therapeutics at Sloan-Kettering, saw a new opportunity to explain what happened by sequencing the whole genome of the woman’s cancer. Just five years ago, decoding and analyzing all 3 billion bases of the DNA from a tumor would’ve been absurdly time-consuming and expen- sive. Now the sequencing takes as little as a few days. Poring over the outlier patient’s genetic code, Solit pinpointed two mutations that made her tumor sensi- tive to this drug. He found that one of her mutations shows up in about 8 to 10 percent of other bladder can- cer patients, meaning that they too might be helped by everolimus. His success has inspired a whole set of ILLUSTRATION BY ELLEN WEINSTEIN 36 HOUSE_OVERSIGHT_015496