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Research Intensifies Towards Personalized Cancer Treatment

Posted on: Tuesday, 17 February 2009, 07:55 CST

A wave of new research is shifting the direction of cancer treatment away from a one-size-fits-all approach towards more tailored therapies based on a tumor’s genetic makeup.

For instance, everyone diagnosed with advanced colon cancer today is advised to get a genetic test before undergoing two of the leading treatments.   The move is a significant change adopted by oncologists last month after research discovered that Erbitux and Vectibix won't work in four-in-ten patients.

Scientists are quickly testing similar genetically tailored therapies for breast and lung cancer.  It's an enormous amount of work that reflects a vast challenge in that most medications today benefit at most only half of patients. 

Unfortunately, it typically requires trial-and-error to discover which patients will benefit, meaning many people suffer side effects and the high expense of treatment for nothing.  

Indeed, when the American Society of Clinical Oncology advised giving colon cancer patients the $300 test for a gene known as KRAS, it estimated the move would save an astonishing $600 million annually by preventing patients who would not benefit from the $10,000-a-month drugs from taking them.

However, as appealing as personalized medicine is, gene testing is uncharted territory.  Laboratories frequently introduce new tests at the first indication they might work, instead of waiting for proof of their effectiveness. And few tests have received the support of major medical organizations such as cancer specialists ASCO.

"A bad test is as dangerous to a patient as a bad drug," Dr. Richard Schilsky, a University of Chicago oncologist and ASCO president, told the AFP.

"The tricky part is to figure out which of those (genetic differences) are clinically important and which are just variations that exist."

The personalized approach to care is not about testing if people carry certain genes that make them more susceptible to illness. Rather, it seeks to find a tumor's genetic fingerprint --a pattern of gene and protein activity that indicates whether the cancer will grow slowly or rapidly, be more or less likely to recur and whether treatments will be effective.

"We're getting into science fiction sort of, if now medicine is being able to analyze things at the genome level," breast cancer patient Claire Weinberg told the AP.

After a community hospital dismissed her breast lump, she sought a second opinion at Duke University Medical Center where she enrolled in a study of gene-directed chemotherapy after receiving a cancer diagnosis.

"I felt it could only benefit me for them to know even more about me," she said.

Dr. Matthew Ellis of Washington University in St. Louis, who co-invented a different breast cancer genetic approach, told the AP that the ultimate goal is to find the right treatment for each individual patient.

"What's the right recipe for those patients?” he said.

A number of areas are currently under study to help personalize cancer care.  For example, a less precise test is currently available that can tell certain breast cancer patients if they are at high or low risk of relapsing, which can help them decide whether or not to proceed with chemotherapy.  However, deciding which chemo is another challenge.  

Dr. Kelly Marcom at Duke University is now genetically profiling breast biopsy tissue from roughly 300 newly diagnosed patients who will soon undergo pre-surgery chemotherapy.  Some are randomly assigned to one of two standard chemotherapy regimens, while the rest will receive a cocktail that matches their tumor’s genetic profile.

It's too early to tell if Dr. Marcom’s approach helps more tumors shrink.

However, "I can have no regrets," says Weinberg, who after her surgery learned she had been assigned to the gene-tailored group.  Her tumor subsequently shrank enough to save her breast.  She's also undergoing post-surgery chemotherapy to kill off any rogue cancer cells that may remain.

In another study unveiled last week, scientists are examining 50 breast cancer genes to discover which of four disease subtypes a woman has. If successful, the Breast Bioclassifier could change the very names of breast cancer.

Researchers studied stored samples of old tumors, and discovered that some women who safely skipped chemotherapy had a subtype of breast cancer that responded better to post-surgery tamoxifen, or hormone therapy. A more aggressive type of breast cancer was sensitive to most chemotherapies but not hormone treatment, the researchers wrote in the Journal of Clinical Oncology.  Another group did not respond well to either treatment and desperately needs new treatment options, Ellis said. 

Ellis worked with doctors at the University of Utah and University of North Carolina, Chapel Hill to develop the test.

Next in the research pipeline is lung cancer, with hospitals across the country now recruiting 1,200 lung cancer patients to study who carries extra copies of the tumor-promoting gene EGFR.  Participants will receive one of two top treatments --Tarceva or Alimta –to determine which is best for a particular genetic condition.

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On the Net:

• American Society of Clinical Oncology
• Washington University in St. Louis
• Duke University

Source: redOrbit Staff & Wire Reports

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