Personal prescription

The one thing Kevin Carlberg refused to face after his diagnosis with brain cancer in 2002 was anyone’s estimate for how long he might live.

His doctors and his family all knew the number: six to 18 months.

“I understand the averages,” says Carlberg, a rock musician who had just released a CD and was two months from his wedding date when he was told he had the worst stage of the worst kind of brain cancer, glioblastoma. “But every person is different.”

Those words could serve as a new mantra in medicine. After having his tumor removed and undergoing chemotherapy and radiation, Carlberg received a novel treatment that was designed using his own white blood cells and proteins taken from his tumor to prod his immune system into recognizing and attacking more cancer. It’s an example of a growing health-care strategy known as personalized medicine.

In the traditional medical model, patients diagnosed with cancer in a particular organ receive the same medications – usually chemotherapy – delivered in an average dose. But some estimates suggest that as many as 70 percent of cancer patients don’t respond to this standard approach. Doctors then go back to the drawing board.

Personalized medicine aims to minimize that one-size-fits-all model by matching each patient to a specific treatment based on the genetic and molecular characteristics of that person’s tumor. Doctors can use genetic information gleaned from the tumor itself to choose – or avoid – certain medications for that patient or, as in Carlberg’s case, create a treatment specifically for that person.

Not so long ago, “most lung cancers were treated the same way; colon cancer the same way. Breast cancer was treated one of two ways,” says Dr. Dennis Slamon, director of clinical and translational research at Jonsson Comprehensive Cancer Center at the University of California, Los Angeles and a pioneer of personalized cancer care. “But that was as sophisticated as it got, and we had huge variations in patients’ outcomes. That should have told us we were dealing with different diseases.”

Personalized medicine is gaining momentum in many areas of treatment. But its greatest application might be in the complex field of cancer, says Dr. Robert Figlin, director of the City of Hope Comprehensive Cancer Center in Duarte, Calif.

“Cancer is a disease which has been misnamed,” Figlin says. “It’s not a disease. It’s hundreds of diseases.”

Personalized medical care is a practical benefit from the Human Genome Project, the 13-year project, completed in 2003, that gave scientists a precision map of the genetic information of humans. Completion of the genome project allowed them to easily locate genetic differences between individuals, including gene variations that cause disease, as well as molecular changes that sometimes turn cells rogue.

“This revolution in molecular biology has translated to understanding … the reasons why cancer grows,” says Dr. Roy S. Herbst, chief of the section of thoracic medical oncology at the M.D. Anderson Cancer Center in Houston.

For example, he says, in traditional practice, doctors removing a tumor send it to a lab to be categorized by size and shape.

But now in some cancers – not yet all – doctors can examine the tissue for specific genes and molecular processes that suggest the cause of a cancer, its potential to grow and what it might take to subdue it.

Personalized medicine – luckily – doesn’t mean that every cancer is unique and must be treated in a unique way, Slamon says. In a group of 1 million people with breast cancer, for example, there are not 1 million types of cancer. Rather, “There may be seven or eight different subgroups,” he says, each with a different molecular cause that warrants a different approach to treatment.

To identify these sub-types of cancer, doctors search for biomarkers, molecular indicators of how that tumor will respond to various drugs. Slamon, for example, worked for more than a decade trying to understand a protein biomarker called HER2.

About 25 percent of women with breast cancer carry a gene mutation that triggers an excess production of HER2. This protein makes the cancer more aggressive and difficult to treat. The discovery led to a drug called Herceptin, approved in 1998, which specifically targets HER2 and decreases cancer recurrences in these women by as much as 50 percent.

Drugs tailored to a particular genetic or molecular mechanism are called targeted therapies because they home in on the biological signature of that tumor. They are often less harsh than standard chemotherapy because they target only the cancer cells without harming healthy cells. For example, therapeutic cancer vaccines, which are being used to treat several types of cancer, are designed to activate the immune system to recognize and kill only cancer cells.

Carlberg’s treatment involved just such a vaccine. To make it, Dr. Linda Liau, director of UCLA’s brain tumor program, isolated proteins from his tumor, mixed it with immune cells from his blood and injected the mixture. The vaccine was designed to prime the body’s immune system to recognize and attack cancer cells.

After six years in remission, Carlberg, 31, recently had another small tumor removed and began receiving chemotherapy and the personalized vaccine therapy again.

Although he had never heard of a cancer vaccine, Carlberg thought the idea sounded brilliant. “It made perfect sense to me,” he says. “Forty years from now I hope I can say I was among the first people to conquer this cancer because of the vaccine. That would be amazing.”

Cancer vaccines have the potential to do more than shrink an already-grown tumor, says Liau, a professor of neurosurgery at the David Geffen School of Medicine at UCLA.

“Once we are able to prolong life through molecular targeted cocktails of treatment, I think the next step is to cure it, by giving something like a vaccine that really tries to get rid of the microscopic cancer cells and prevent the cancer from coming back.”

Personalized cancer treatments are being tested in many types of cancers, particularly those most difficult to cure.

Lung cancer, which strikes 215,000 Americans a year and kills almost 162,000, is one area of rapid advancement. Doctors are now looking at several biomarkers that can dictate the course of treatment, says Dr. Karen Reckamp, assistant professor of medical oncology and hematology at City of Hope.

Tarceva is a targeted therapeutic drug that has extended the lives of many people with advanced nonsmall cell lung cancer. But about 25 percent of people with such lung cancer have mutations in a gene called KRAS. In people with this mutation, Tarceva is ineffective.

“In the last five years, we understand the biology of lung cancer significantly better than we ever did,” Reckamp says. “This means that we can give the appropriate drug or treatment to the appropriate person at the right time.”

Patient safety is another bonus of personalized therapy. For example, researchers have found that some children with acute lymphoblastic leukemia carry a gene mutation that causes a standard drug used to treat the disease to build up in the body and cause dangerous side effects. These children are identified before treatment begins and receive smaller doses to prevent toxicity.

As cancer specialists learn more about the variability of tumors, some of the news they give patients isn’t good. Personal cancer care sometimes means that patients are told a particular drug – often promising for some people – will not work for them.

“People think of personalized medicine as ‘If my doctor knew what I had, the results of the treatment would be better.’ That is our hope as well,” Figlin says. “But the reality is we also identify genetic abnormalities in cancer that predict why a certain treatment may not work.”

Nonetheless, after a slow start, the field of personalized medicine is gathering steam as researchers and drug companies focus more on drugs to target subsets of patients instead of blockbuster medications aimed at treating all of them. According to the research company Datamonitor, sales of targeted cancer therapies grew 33 percent worldwide last year. Since 2005, 10 targeted drugs have come on the market.

Slamon spent years trying to persuade others that targeting HER2 would cure some women of breast cancer. Eventually, the drug company Genentech developed Herceptin.

“Drug development is becoming more complex and more challenging as we understand more,” Slamon says. “But that is how it has to be if we’re going to treat cancer more effectively.”