On a leafy hillside along the north shore of Long Island, a team of scientists digs deep into cancer cells, searching for an Achilles' heel.
By tinkering with nucleic acids, the researchers at Cold Spring Harbor Laboratory in Huntington have learned to systematically disable individual genes, hoping to find what makes cancer cells go haywire. If they pinpoint the right stuff, they might hand drugmakers a bull's-eye to stop a cancer.
"We are in the business of drug-target identification, mining the whole genome and looking for vulnerabilities," said Dr. Christopher Vakoc, who leads a group of researchers studying leukemia.
Vakoc and his team are among those at Cold Spring Harbor in the vanguard of finding better ways to diagnose and treat diseases that have long outwitted medicine. For generations, doctors have attacked cancers with scorched-earth treatments involving surgery and toxic chemotherapy, which obliterates good cells along with bad and leads to brutal side effects.
Over the last decade, doctors have turned to genetics for more targeted treatments, hoping to neutralize renegade genes without exposing patients to a gantlet of surgery and chemo. But success is often short-lived as cancers mutate and roar back.
Vakoc came to Cold Spring Harbor in 2008, drawn in part by the lab's pioneering work to genetically engineer mice, allowing researchers to give them human cancer genes and watch how the disease mutates and evades treatment, just as it does in people. One of his first projects was hunting for proteins that help control those mutations in acute myeloid leukemia, which kills 75 percent of patients within five years.
Using technology developed at Cold Spring Harbor, Vakoc and his team screened hundreds of proteins that the body uses to switch genes on and off. One particularly struck them: Brd4. If shut off, it appeared to stop the cancer cold. "It was this super Achilles' heel," Vakoc said.
While scientists can genetically turn off mouse genes, they need a drug to do it in humans.
It turned out, however, that the Dana-Farber Cancer Institute in Boston had been developing drugs targeting Brd4, hoping they'd work against cancer. Vakoc's lab teamed up with the group at Dana-Farber to successfully test them against leukemia in animals. Later this year, several companies plan to start testing the drugs in humans.
Meanwhile, Vakoc and his team are working with other researchers and drugmakers -- including Stony Brook-based startup Coferon Inc. -- to pinpoint additional targets.