Moffitt Cancer Center decodes cancer

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TAMPA — After learning her ovarian cancer was back, Lois Kreditor faced what amounted to a medical game of roulette.

Only a handful of drugs were available, and her doctors knew most wouldn't work. Trial and error was the best they could offer the 46-year-old mother of three.

So they referred her to H. Lee Moffitt Cancer Center & Research Institute in Tampa, where researchers are building a frozen bank with tens of thousands of cancer samples. After years of development, they are now decoding the genetic finger­print that makes each cancer unique, hoping to match patients with the drugs that could save them.

Kreditor, who lives in west Palm Beach County, became Patient One in a clinical trial testing scientific theory against the brutal realities of cancer treatment.

If genetic profiling led doctors to the right drug immediately, Kreditor would be spared weeks of harsh drug therapy that might not work anyway.

If doctors got it wrong, her prognosis would remain grim: Only one in 10 patients with her stage of ovarian cancer respond to treatment. Perhaps five percent go into complete remission.

Moffitt Cancer Center believes it is on the vanguard of research institutions betting that understanding the genetics of cancer will lead to more effective treatment, not just for Kreditor but for scores of patients. State and local governments have invested millions in this vision.

But first, researchers need to find the Achilles heel in many types of cancers. Only then can medicine deliver on the bold promise of personalized cancer care: No more standard regimens that treat all patients with, say, lung cancer, as if having a tumor in the same organ made them all the same.

"There's no guarantee you're going to respond to that regimen. In fact, in some cases, there might be only a 30 to 50 percent chance that you'd respond," said Dr. Timothy Yeatman, president and chief scientific officer of M2Gen, the Moffitt spin-off leading the effort. "We'd like to change those odds."

Where it goes awry

Profiling cancer amounts to deconstructing a car wreck. But this accident happens microscopically, in the body's essential building blocks.

Every cell takes its marching orders from the famous double-helix at its core, the DNA, which is embedded with a set of instructions, or genes. The genes tell cells what to produce. They dispatch their message by copying their information onto a strand of RNA.

In cancer, something along this chain of events goes awry.

Three decades ago, scientists peered at cancer cells under a microscope and wondered why they looked different. Today's tools are exponentially more powerful. Top researchers can see which of the 30,000 genes in a tumor cell are turned on or off.

The Human Genome Project, completed in 2003, gave researchers a map to help pinpoint the genetic abnormalities and mutations that allow cancer to spread. Many believe this information will lead to developing more effective therapies.

"The analogy with people is it really doesn't matter where somebody was born, right? It matters who they become," said Dr. Robert Wenham, director of gynecologic oncology at Moffitt. "We know that with people, but we're just trying to do that with cancers."

Wenham designed a clinical trial aimed at bridging the gap between laboratories and patients' bodies.

His first patient: Kreditor.

The challenge: Analyze her tumor in time to find the treatment that would halt her cancer.

Searching for patterns

Moffitt has a lot of experience doing genetic profiles for research. In the past three years, it has collected about 10,000 tumor samples from patients willing to contribute to the bank it is building. Each tumor was analyzed in a process similar to that used for Kreditor.

A sample of the tumor is extracted and "snap frozen'' with liquid nitrogen to negative-190 degrees Celsius to preserve the fragile RNA. (DNA samples, by contrast, can survive for ages under all kinds of conditions, which is why you hear about DNA in crime-scene analysis.)

Powerful computers then read the DNA or RNA markers, which scientists bind to a silicon chip.

On the computer screen, the genes look like a fuzzy television screen. Magnified they are a checkerboard with thousands of light and dark squares. Light is on — the gene is expressed, or active. Dark is off.

It looks like a Lite-Brite toy, only illuminating the genetic expressions of cancer.

Patterns emerge across scores of cancer samples, potentially leading to important discoveries.

Consider the HER2 gene. Too much of it gets expressed in about 20 to 30 percent of breast cancers, the ones long considered the most aggressive to treat.

But when a specific drug, Herceptin, is added to the best chemo­therapy regimens, survival rates for these patients approach 90 percent, rather than about 65 percent with chemo alone.

This discovery saves the lives of about 7,000 American women every year.

"A new biological breakthrough is not a cure, but we need it," said Tracy Lively, associate chief of the National Cancer Institute Diagnostics Evaluation Branch, which helps researchers to develop lab tests for clinicians.

"And in some forms of cancer we are really starting to see the changes in outcome — meaning that people are living longer and recovering their health — that we want to see for everybody."

Matching therapies

The search is on to find the HER2's of other cancers. In colon cancer, doctors now know that the K-ras genetic mutation can indicate whether a patient will respond to a key drug. In lung cancer, specific molecular abnormalities can be guides to the best treatment options.

Massachusetts General Hospital, a primary teaching hospital for Harvard medical school, recently announced plans to begin genetic testing for all cancer patients. They start this spring with lung cancers.

"There certainly are many people diagnosed with cancer for whom with current technology we won't be able to find a genetic abnormality for which we can say, 'Ah-ha, here's the therapy for you,' " said Dr. Leif Ellisen, director of Mass General's translational research laboratory.

But advances are building, one clinical trial at a time.

Checking results

At Moffitt, only two patients have entered for the ovarian cancer study, which is recruiting the most difficult to treat cases. One day, Moffitt hopes to tap its cancer bank to quickly reach patients who might be helped by a promising new trial or drug therapy.

The first patient, Kreditor, knew something was wrong when her abdomen suddenly swelled so much, her Size 4 clothes no longer fit. That was two years ago. She received chemo­therapy and surgery.

But the cancer came back, and Kreditor came to Moffitt for a diagnosis and a treatment plan, which she took back home.

Now Patient One is cancer-free.

Kreditor again is playing tennis and exercising daily. She runs errands with her twin teenage daughters and 10-year-old son.

Only time will tell whether Moffitt can repeat those results in many more patients, which could lead to a breakthrough in ovarian cancer treatment.

Certainly, Patient One is a promising start.

Letitia Stein can be reached at lstein@sptimes.com or (813) 226-3322. For more health news, visit www.tampabay.com/health.

FAST FACTS

Total Cancer Care at Moffitt: A frozen cancer bank

Patients donate a specimen from the tumors removed during routine biopsies and share their medical histories. Today, Moffitt uses the information for research. Through the M2Gen venture, it also hopes to make money by partnering with companies who are developing new cancer drugs. Eventually, Moffitt plans to contact patients when new treatments become available.

By the numbers

30,000 participating patients

10,000 tumor specimens (not all patients have tumors removed)

2.5 million sample capacity, including blood and urine

Ovarian cancer symptoms

This year, about 22,000 women in the United States will learn they have ovarian cancer. Nearly 15,000 women will die of the disease, the fifth-leading cause of cancer deaths in women, according to the American Cancer Society. About two-thirds are 55 years or older.

Symptoms include:

• Swelling of the stomach

• Stomach pain

• Trouble eating or feeling full quickly

• Having to urinate often, or feeling great urgency to do so

[Last modified: Jun 05, 2009 05:21 PM