Method created to personalize chemotherapy drug selection

Scientists have developed a way to personalize chemotherapy drug selection for cancer patients by using cell lines created from their own tumors. If proven further, this technique could replace current laboratory tests to optimize drug selection that have proven technically challenging, of limited use, and slow.

Oncologists typically choose anticancer drugs based on the affected organs' location and/or the appearance and activity of cancer cells when viewed under a microscope. Some companies offer commercial tests on surgically removed tumors using a small number of anticancer drugs. But Anirban Maitra, MBBS, of Johns Hopkins University School of Medicine in Baltimore, Maryland, said the tissue samples used in such tests may have been injured by anesthetic drugs or shipping to a lab, compromising test results. By contrast, he said “our cell lines better and more accurately represent the tumors, and can be tested against any drug library in the world to see if the cancer is responsive.”

The scientists developed their test-worthy cell lines by injecting human pancreatic and ovarian tumor cells into mice genetically engineered to favor tumor growth. Once tumors grew to 1 cm in diameter in the mice, the scientists transferred the tumors to culture flasks for additional studies and tests with anticancer drugs.

In one experiment, they successfully pinpointed the two most effective anticancer drugs from among a library of more than 3,000. These two drugs were the most effective in killing cells in one of the pancreatic cancer cell lines. This research was published in Clinical Cancer Research (2013; doi:10.1158/1078-0432.CCR-12-2127).

The new method was designed to overcome one of the central problems of growing human tumor cell lines in a laboratory dish—namely the tendency of noncancerous cells in a tumor to overgrow cancerous ones, said James Eshleman, MD, PhD, also at Johns Hopkins. As a consequence, it has not been possible to conventionally grow cell lines for some cancers. Still other cell lines, Eshleman said, do not reflect the full spectrum of disease.

To solve the problem of overcrowding by noncancerous cells, genetically engineered mice were bred that replace the noncancerous cells with mouse cells that can be destroyed by chemicals, leaving pure human tumor cells for study.

“Our technique allows us to produce cell lines where they don't now exist, where more lines are needed, or where there is a particularly rare or biologically distinctive patient we want to study,” said Eshleman.

In its proof-of-concept research, the team created three pancreatic ductal adenocarcinoma cell lines and one ovarian cancer cell line. Then one of the pancreatic cancer cell lines (Panc502) was tested against their library of 3,131 drugs, identifying tumor cells most responsive to the anticancer drugs digitoxin and nogalamycin.

For 30 days, they watched the effects of the two drugs in living mice and a control medicine on tumors derived from Panc502 and a control pancreatic cell line. Both drugs demonstrated more activity in reducing the tumor appearance and size in Panc502 than in the control line, supporting the notion that the cell line technology may better predict sensitivity to the two drugs.

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