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ADVANCED GENOMIC TESTING

Genomic medicine: The future of cancer treatment is now

Cancer care has made great strides over the past decade, and three little letters have made a huge difference in the journey: DNA.

Like detectives working a cold case, scientists are using genes to unravel the mysteries of cancer's origins and mutations, unearthing clues to a disease of genetic mistakes. The burgeoning field is called genomic medicine, and it is equipping doctors with new tools to target cancer at its source: the blunder coded in its molecular structure.

Much of the progress has come in mapping a patient's cancer cells. Just as every person is different, cancers have their own personalities, too, behaving, growing and mutating according to the dictates of the code mapped out in the tumor's DNA. Think of DNA as an instruction manual. It tells your heart how to pump, your brain how to think and your bones how to grow.

Every cell in your body has a complete strand of DNA, and packed into each winding molecular string are an estimated 20,000 to 25,000 genes. They determine everything from the texture of your hair, to the slope of your jaw line, to your risk for disease and how your body responds to drugs.

As we grow and age, new cells form. They're created by DNA replicating itself, copying and transmitting its exact sequence to every baby cell. It's a complicated process, and sometimes, it goes awry, spawning coding errors, or "misspellings" in the gene. The vast majority of the time, our bodies fix the errors on their own, often immediately.

Errors that aren't fixed become permanent mutations, which behave differently in cancer cells than in other cells of the body. Mutations can also be passed down from parent to child, or created through environmental or spontaneous influences. Many are harmless, but when mutations tell the tumors to act in insidious ways, cancer forms. Because of some coding errors, for example, cancer cells never get the signal to stop dividing. Other mutations tell the cells to grow aggressively. Mutated BRCA1 and BRCA2 genes, which have been linked to some breast cancers, produce fewer tumor-suppressing proteins that repair damaged DNA.

Just as your genome can be sequenced to identify your unique genetic makeup, decoding cancerous cells can reveal why they're acting the way they do, and perhaps how to stop their errant behavior. Genomic sequencing is typically reserved for patients with advanced cancers that haven't responded to traditional treatments like surgery, chemotherapy and radiation therapy, which are effective for most patients. The process of decoding a patient's genome starts in the lab, where "we are able to use highly sophisticated, highly sensitive equipment to look at tumor abnormalities at a molecular level," said Dr. Maurie Markman, President of Medicine and Science at Cancer Treatment Centers of America® (CTCA).

Technicians sequence the DNA obtained from a biopsy of the tumor, then scan it for abnormalities. Certain mutations, especially those common to lung, breast and colorectal cancer, have been studied closely over the years, giving oncologists a better understanding of their behaviors—and their response to treatments. If the abnormalities found in the patient's tumor match known mutations, oncologists can recommend therapies that tend to be effective for that particular malignancy.

"Ideally, it would be great if we had one disease, with one mutation, with one treatment, with one drug, but unfortunately, that's not the case," said Dr. Shayma Kazmi, Medical Oncologist and Hematologist at CTCA. "For people who have one of the identifiable mutations, if we can target that with treatments that have been known to work elsewhere, perhaps we can have better outcomes."

The discoveries are helping to refine the approach to cancer treatment. Oncologists, for example, have found similarities in the genetic makeup of different types of cancer. One patient's lung tumor, say, may look and act much like an abnormality more typical in breast cancer. This revelation can open up new possibilities for drug therapies that may not have otherwise been considered in that patient's treatment plan.

"That's when it gets really interesting," Dr. Kazmi said.

The targeting process is so precise that the field has earned a new name: precision medicine. And cancer specialists like Kazmi predict it will lead to a day when cancer is no longer defined by where it's located—pancreatic cancer in the pancreas, liver cancer in the liver—but by the molecular structure coded in its DNA.

The expanding landscape is bringing new prospects, and new opportunities. As knowledge of genomic medicine has increased, its cost has plummeted. Sequencing a human genome today costs less than $10,000, compared to more than $100 million in 2001. Not only are the tests more available to patients, but more oncologists are trying their hand at tumor testing and building on the base of knowledge. And, in January, the field got a major boost when President Obama announced the $215 million Precision Medicine Initiative to get even more scientists to dig into genetic causes for disease and find new drugs to target mutations.

"As much as it is a really promising future, it's a really exciting to be part of the changing landscape," Dr. Kazmi said of genomic profiling for cancer patients.

And yet, there are still many unknowns. For example, one tumor may spawn several varying mutations, and they all may interact differently depending on the patient. Scientists don't yet know why that is, or for that matter, why some abnormalities lead to cancer and others don't.

"Is cancer in one place going to behave the same way as the metastatic cancer in another place?" Dr. Kazmi said. "We haven't answered these questions yet."

But the prospects for discovery are bright. Those who dedicate their lives to understanding cancer say there is no overestimating the potential for genomic medicine to dramatically improve the diagnosis, treatment—and prevention—of cancer.

"This is an incredibly powerful, positive force in medical care. We were in the Dark Ages before this," Dr. Markman said. "It is the tsunami on our shores, and it's going to take over all of medicine. This is not a trend; it's the future of medicine. There's no question about it."

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