Cancer-gene analysis customizes treatment

Anna Paternoster, a cancer survivor, at her home

Anna Paternoster, a cancer survivor, at her home in Laurel Hollow. (July 8, 2011) (Credit: John Dunn)

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Anna Paternoster took her doctor's advice and sought treatment more than a thousand miles from home for her aggressive cancer, and in the process is helping scientists break new ground in their understanding of the genetics -- and treatment -- of ovarian cancer.

Paternoster's therapy grew out of the worldwide race to save lives by identifying the cancer's genetic signature and creating highly specialized drugs to block mutant DNA.

The medication under study, doctors say, is a near molecule-for-molecule match against the forces driving the disease.


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Paternoster, 46, of Laurel Hollow, has been flying between New York and Florida once a month since January, undergoing therapy in a clinical trial at Moffit Cancer Center in Tampa, the closest test site. Her cancer was diagnosed six years ago.

"I told my doctor I would be willing to travel anywhere in the world. It didn't matter where, because I am doing this for my children," said Paternoster, a married stay-at-home mom with three school-age children.

 

Genetically defining disease

Her Tampa trips -- she's usually on a plane before dawn and not home until 7 at night -- are not only keeping her cancer at bay, they're helping medical investigators usher in an era of customized medicine.

"We want to keep moving this idea of individualized medicine forward," said Dr. Douglas Levine, a physician-scientist at Memorial Sloan-Kettering Cancer Center in Manhattan and Paternoster's doctor.

Just as there's no single gene that triggers all forms of cancer, Levine said, there's no single therapy that equally treats all cancer patients, even though chemotherapy has been based on a one-size-fits-all approach for decades.

The exploration of cancer genetics, he said, is unmasking vulnerable genes and producing new therapies.

Paternoster's treatment, called PARP, exploits a specific DNA instability in a type of ovarian cancer called serous adenocarcinoma, which accounts for about 85 percent of all deaths. PARP, Levine said, induces ovarian cancer cells to die.

Ovarian cancer has one of the lowest survival rates for any form of cancer. The National Cancer Institute estimates 21,990 women will develop the cancer this year and 15,460 will die of the disease.

There's an outside chance Paternoster's cells will "learn" to repel the medication, making the drug useless. But for now, Levine said, everything is working well.

Knowing which DNA to target, Levine said, grew out of The Genome Atlas of Cancer, a massive undertaking launched in 2005. Scientists examined 316 ovarian tumors to genetically define the disease.

Led by National Cancer Institute scientists, the project included contributions from researchers at Sloan-Kettering and Cold Spring Harbor Laboratory.

The investigation's findings, reported earlier this month, are among the most comprehensive for any form of cancer. Plans are under way for 20 additional atlases on other malignancies.

 

New view of cancer

Dr. Alexander Krasnitz of Cold Spring Harbor Laboratory said identifying genetic signatures can lead to a paradigm shift in what's known about a cancer. Years of studying breast cancer genetics, he said, have revealed that it's multiple diseases, not simply one.

In ovarian cancer, scientists found mutations in a single gene dubbed TP53. The mutations were present in more than 96 percent of tumors tested.

To find a potential treatment, investigators searched drugs already government-approved and capable of inhibiting aberrant DNA associated with the disease. The search led to PARP.

Twenty PARP clinical trials involving hundreds of patients are under way nationwide. The drug is being tested alone or in combination with conventional chemotherapy.

"We had known about many pieces in the puzzle," Levine said, "but in the past, many parts of the puzzle had blurry edges. We have now taken a giant leap forward."

Paternoster's cancer was discovered in 2005 during a routine exam while she was pregnant with her third child. "I went in for my 20-week sonogram, and the doctor noticed a small growth on my right ovary," she said. A series of tests after her baby's birth confirmed the cancer.

Over the years, Paternoster said, she's struggled through chemotherapies that made her feel sick. Today she feels much better, thanks to PARP, which involves taking one pill a day.

In Florida she undergoes blood tests and scans aimed at detecting possible recurrences.

"The drug and the tests are the only expenses they cover. I have to pay for the travel," Paternoster said. "When it's your life, you find a way to do what you have to do."

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