Healthy Living: Cancer

 

If you must have cancer, this is not the worst time to have it.

Technological advances have greatly increased survival rates; there are new treatments with fewer side effects and drugs that manage those side effects that still can’t be avoided. Public awareness campaigns have taken a lot of the mystery and some of the fear out of a cancer diagnosis, and efforts like Avon’s Walk for a Cure and Norwalk Hospital’s Wittingham Cancer Center Sally’s Run have raised hundreds of thousands of dollars for cancer research every year.

But what’s really promising in the fight against cancer—and slightly awe-inspiring—is the ongoing research into the curious travels and adventures of our body’s molecules, cells, genes and proteins. It is a world in which there are: nice white blood cells whose job it is to search out infections and eradicate them; red blood cells, which carry necessary oxygen around in our bodies; messenger molecules that carry instructions to lymph nodes and DNA that stores the information for our bodies; and T-cells, B-cells, scavenger cells and dendritic cells—all working in a highly choreographed dance to keep us growing hair and skin, breathing, fighting viruses, digesting food, and even defending against cancer.

But they are not so orderly that we don’t get a “bad boy” cell once in a while, one that decides to attach itself to the wrong protein or divide without provocation, and once loose, can wreak havoc in our immune system. It turned bad because of something toxic in its cellular life, or maybe just because it felt like it. It turned bad, then precancerous, then cancerous, and then it made a tumor. It’s like any bad boy, which means sometimes we can never figure out why it does what it does.

But these days if we know where it is and what it’s doing, we can often stop it—or at least slow it down.

And herein lies the core of current oncological research: searching out the patterns of cellular mutations that cause cancer and then matching those mutations with drugs that will arrest, slow down or even cure—without killing off healthy cells, often eliminating the need for chemotherapy and radiation. Good news indeed!
 

Connecticut is home to two research-intensive academic medical centers: One is Yale-New Haven Hospital’s campuses in and around New Haven, the other is the University of Connecticut Health Center in Farmington, where the Carole and Ray Neag Comprehensive Cancer Center is located. Both conduct research on cell mutation and the drugs that can do something about it.

The Yale complex is quickly growing into a sprawling minicity of cancer research and care under the passionate direction of Dr. Thomas J. Lynch Jr., a pioneer in the use of molecular testing and targeted drugs for lung cancer. There is the impressive, comprehensive Smilow Cancer Hospital, which opened in 2009, and now there is also Yale’s West Campus, snapped up in a real estate transaction in 2007 that Yale’s PR department likes to call “the deal of the century,” when Bayer Pharmaceutical Co. decided to pull up stakes and leave Connecticut.

Purchasing a facility used for manufacturing drugs and conducting research was indeed a coup. The high-tech scientific infrastructure Yale wanted was already in place. The labs in the newly christened Cancer Biology Institute were already outfitted with equipment needed to conduct genome analyses, research cell biology and study the effects of small molecules on cell functions. The new Center for Genome Analysis has a battery of cutting-edge, state-of-the-art DNA sequencing machines, the most comprehensive in southern New England. The institute is now under the direction of Joseph Schlessinger, Ph.D., whose résumé includes cofounding three biotech companies.
 

 

“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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