An Israeli hospital's bone-marrow bank is forming the cutting edge in efforts to adapt drugs to each patient's genetics.
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Storing tissue in bone-marrow cancer – myeloma – is more challenging than in cancers with more solid tumors such as breast cancer or colon cancer. But a study launched in October 2012 in four centers around the world – including Israel's Sheba Medical Center – uses new technology to separate diseased cells from healthy ones.
“It’s not easy to set up a tissue bank for myeloma because before the tissue … can be stored, the diseased and healthy cells must be separated so that we only keep the diseased cells,” say Dr. Merav Leiba, head of the multiple myeloma clinic and myeloma research lab at Sheba’s hematology institute.
The diseased cells are then kept at minus 80 degrees so they can undergo genetic scanning.
“Unfortunately, there are no myeloma treatments adapted to a genetic mapping of the tumor, but in the future, when such treatments are available, we can adapt them to patients based on mapping their frozen tissue, without having to extract new tissue,” Leiba says.
New anti-cancer drugs only shrink the tumors of patients with particular mutations. Some of these drugs are included in Israel's government-subsidized "health basket" for carriers of these mutations.
For example, Herceptin against breast cancer is only effective in patients carrying a mutated tumor gene called HER-2. Erbitux is effective in colorectal-cancer patients who do not have a mutation in the tumor gene K-RAS. And Tarceva and Iressa do well in lung-cancer patients with a certain mutation in the tumor’s EGFR gene.
A March 2011 report in the journal Nature Medicine described a genetic sequencing of myeloma patients. In 5 percent to 10 percent of the patients, a mutation in the BRAF gene allows for customized treatment. Patients who allow their tissue to be frozen also receive a genetic scan that costs thousands of dollars.
Bone-marrow cancer involves growths in certain bone-marrow cells; these cells secrete substances that damage the bones and cause pain and fractures. Today, drugs are the primary treatment, though sometimes radiation or a self-transplant of bone marrow is required.
Myeloma is not a very common cancer, afflicting 4.2 people per 100,000 a year, with about 300 new patients in Israel annually. New drugs are extending the lives of patients by 10 years on average, up from the previous two to three years.
No pathogen has been identified with certainty, though in the United States myeloma is more frequent among African-Americans, and there is evidence linking the disease to exposure to pesticides and chemicals such as benzene.
Another study at Sheba found that myeloma is twice as common among Ashkenazi Jews as among Jews with roots in Spain, North Africa or the Middle East. There is a particularly low incidence among Jews of Iraqi and Yemenite origin.
“We believe that the explanation for the differences in disease incidence by origin is genetic rather than environmental, because by the third generation most Israelis have been exposed to the same diet and the same environment and conduct a similar lifestyle," says Leiba.
Sheba is currently experimenting with two new drugs against myeloma. One, being tested in collaboration with Teva Pharmaceutical Industries, has produced good results. The other, not yet in clinical testing, is produced from a plant that grows in China.