Healthy Living: Cancer


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“There’s something new every day,” says Dr. Jeffrey Sklar as he sits at a dark mahogany conference table with his colleague Dr. Zenta Walther in a small room overlooking Cedar Street on Yale’s downtown New Haven campus. They are a charming twosome—avuncular Sklar with his bright silver hair and incongruously black eyebrows, Walther who looks more like a debutante than an associate professor of pathology with both an M.D. and a Ph.D. Their talk is spirited and medically, biologically complex.

Their work, they explain, begins with what is called “tumor profiling.” After a tumor has been removed, it goes straight to the lab. If certain genetic mutations can be identified, it can be determined which drugs will be effective.

 “PLX4032,” interjects Walther, offering an example of a new drug that fights melanoma. “The clinical trial results are so good they’re expecting an early approval.”

Tumor profiling and genomic analysis provide the information needed to match up mutations with the right combination of drugs. When they talk about how this all came about—the early experiments, the unexpected advances—Sklar and Walther look as though they’re recalling the plot of an especially good movie, one in which the action is played out on a set the size of a pin point.   

Genome analysis and DNA sequencing were in their nascent stages when Sklar was in med school. He was studying bacteria. When President Nixon withdrew federal funding for the program Sklar was enrolled in, the Connecticut Mutual Life Insurance Co. stepped in to provide funding—but for only one student per institution.

“I realized I had to come up with something that would set my application apart from everyone else’s.” Retelling the story, Sklar smiles. “I was thinking, how do I justify my work on bacteria?

“So I wrote, ‘If we can understand how genes work in bacteria, then someday we can understand cancer.’ It was a long shot, but I figured that they would forgive such presumption because I was young and naïve.”

He got the slot.

And he was prescient, too. Sklar is now professor of pathology and laboratory medicine at Yale-New Haven Hospital as well as director of the Molecular Diagnostic Program, the Molecular & Genetic Pathology Fellowship and the Tumor Profiling Service.

“Are we there yet? How close are we?” Dr. Anees Chagpar, surgeon and the director of the Breast Center at Smilow, doesn’t even wait to enter her office before answering her own questions regarding breast cancer treatment. “There’s an explosion in cancer research!” she exclaims.

Behind her are brochures announcing the first Closer to Free Bike Ride fundraiser for Smilow. The room is empty at 6:30 p.m., but there is no sign that she is going home soon.

“Look how far we’ve come,” she says, waving her long fingers in the air. “In the ’60s, if you had breast cancer, you had a mastectomy—and they removed all of the lymph nodes under your armpit, too. Now you can get a lumpectomy and a sentinel-node biopsy and you’re home. Already there is a shortened radiation therapy done in five days instead of six weeks and soon we may be able to do it all in one shot.”

Her work, too, is concentrated on molecular analysis, but she wants it to be clear that, in her opinion, none of the progress in breast cancer treatment would have come to fruition if it weren’t for the courage and conviction of the patients who are willing to participate in clinical trials. “We couldn’t do any of this without them,” she says.

Dr. Andrew Arnold, director of the Center for Molecular Medicine and chief of the Division of Endocrinology at UConn Health Center (UCHC), explains the need for more research and more data: “We might find one little DNA change in the lab that altered the corresponding protein by a single amino acid out of hundreds, and we don’t know if it’s a benign and meaningless variant, or is pointing us to a hugely crucial new target. A mistake could be devastating. So we look for more data. The more data, the better you can make an intelligent conclusion. A great deal of research will need to be done to sort out these issues, but it will be worth it.

“I’ve been doing this for 25 years,” he says. “I’ve seen the field develop and everybody is excited about exploiting the genome information—and finally, finally, it’s become affordable to mainstream researchers.”

Dr. Richard Everson agrees. “The cost of DNA sequencing has gone way down,” he says, “and we now know so many possible molecular structures because of the Human Genome Project.” Everson is the director of the Cancer Prevention Program and deputy director for Cancer Control at UCHC.

“How do we identify the 15 percent of patients who might respond to a certain drug?” asks Dr. Mario Sznol, vice chief of medical oncology at Yale. Like Everson, he admits more data is needed, but he’s optimistic and talks about immune therapy as the next big step in the search for a cure. “If we can activate the immune system, we can prevent cancer in the first place. In the next five years, this will really take off. “

How close are we? was Chagpar’s question. Arnold believes we’ll get there, but perhaps not as soon as the hype would have us believe, while Sznol says we’re getting better—and closer—all the time.

Healthy Living: Cancer

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