And this has important implications for Philanthropy, cancer experts say. Support groups should move from fund-raising for cancers in particular to push for research aimed at many cancers at once, said Dr. Brawley. John Walter, chief executive officer of the leukemia and Lymphoma Society, agreed, saying that by pooling forces "our strength can be leveraged." At the heart of this search for new cancer drugs are patients like Joe Bellino, who was an employee of the post office until his cancer made him too ill to work. Seven years ago, he went to the hospital for a hernia surgery, only to learn that he had a rare cancer, liposarcoma of the adipose cells. A large tumor was wrapped around a wire that connects the testicle in the abdomen. "I was shocked," he said in an interview this summer.
Companies have long ignored liposarcoma, not seeing no market for drugs to treat a cancer that affects so few. But it's ideal for drug testing of Sanofi, because the tumors are almost always the exact genetic drugs problem was to attack — a merger of two large proteins. If the drug works, it should bring these tumors raging a setback. Then Sanofi would you test the drug on a wide range of cancers with a similar genetic alteration. But if the drug fails against liposarcoma, Sanofi grudgingly admit defeat. "For us, this is a go/no-go," said Laurent Debussche, a scientist from Sanofi leads drug company seeks.
The genetic alteration of drug targets has tantalized scientists for decades. Normal healthy cells have a mechanism that tells them to die if their DNA is damaged too badly for repair. Cancer cells grotesquely damaged DNA, so ordinarily you would self-destruct. A protein known as p53 that Dr. Gary Gilliland of Merck called Angel of death cell normally sets things in motion. But cancer cells deactivate p53, or directly with a mutation, or indirectly, by attaching the p53 protein to another cellular protein that blocks. The dream of cancer researchers has long been to revive p53 in cancer cells that die on their own. P53 's story began in earnest about 20 years ago. Excitement ran so high that, in 1993, Science magazine has anointed the molecule of the year and put him on the cover. An editorial gave the possibility of a cure for a dreaded killer in the not too distant future ".
Companies began hunting for a drug to restore p53 in cells where it has been disabled by mutations. But while scientists know how to block genes, they haven't figured out how to add or restore them. Researchers have tried gene therapy, adding good copies of the p53 gene in cancer cells. That did not work. Then, instead of going after the mutated p53 genes, they went after half the cancers that used the alternative route to disable p53 by blocking linking it to a known protein like MDM2. When they stick together the two proteins, the protein p53 doesn't work anymore. Maybe, the researchers thought they might find a wedge between the two myself proteins and raise their share.
The problem was that both proteins are enormous and cling tightly to each other. Drug molecules are generally very small. How could find one that would separate these two bruisers, like a referee in a boxing match? In 1996, researchers at Roche has noticed a small pocket between the colossi where a small molecule could slip and pry them apart. It took six years, but Roche found such a molecule and named Nutlin because the lab was in Nutley, NJ
But Nutlins didn't work as drugs because they were not absorbed into the body. Roche, Merck and Sanofi persevered, testing thousands of molecules.
At Sanofi, the stubborn avant-garde scientist, Dr. Debussche, maintained an obsession with p53 for two decades. Finally, in 2009, his team, along with Shaomeng Wang at the University of Michigan and a biotech company, Ascenta Therapeutics, found a promising compound. The company tested the drug every day pumping in the stomachs of mice with sarcoma.e
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