Personalize chemo with cells created from tumor

JOHNS HOPKINS (US) — Scientists have developed a better way to match cancer patients to the drugs that will work best against their particular disease.

The technique, demonstrated so far in lab studies and in mice, would use cell lines created from the patients’ own tumors to test possible chemotherapy regimens. If successful in further studies, the method could replace lab tests that are technically challenging, slow, and of limited use, researchers say.

Oncologists typically choose a patient’s anticancer drugs based on the affected organs and on the appearance and activity of cancer cells seen under a microscope.

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Some companies test surgically removed tumor tissue for its response to a small number of cancer drugs. But Anirban Maitra, professor of pathology and oncology at the Johns Hopkins University School of Medicine, says the samples used in such tests may be injured by anesthetic drugs or by shipping to a lab, compromising test results.

By contrast, he says “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.”

Researchers made the new cell lines by injecting human pancreatic and ovarian tumor cells into mice genetically engineered to favor tumor growth. Once the mice tumors grew to 1 centimeter in diameter, the scientists transferred the tumors to culture flasks for additional studies and tests with anticancer drugs.

In one experiment, they pinpointed—from among more than 3,000 options—two anticancer drugs especially effective in killing cells from a particular pancreatic cancer cell line. A report was published online Jan. 22 in the journal Clinical Cancer Research.

The new method is designed to overcome a central problem in growing human tumor cell lines in a laboratory dish—the tendency of noncancerous cells in a tumor to overgrow cancerous ones.. says James Eshleman, professor of pathology and oncology. As a consequence, it has not been possible to conventionally grow cell lines for some cancers. Other cell lines, Eshleman says, don’t reflect the full spectrum of disease.

To solve the problem of overcrowding by noncancerous cells, Maitra and Eshleman bred genetically engineered mice 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,” Eshleman says.

In the proof of concept research reported online in the journal, Clinical Cancer Research, the team used its method to create a pancreatic ductal adenocarcinoma cell line, Panc502. The cells appeared, from tests against the Johns Hopkins Drug Library of 3,131 drugs, to respond best to digitoxin and nogalamycin.

The researchers then implanted tumor cells from Panc502 and another pancreatic cell line, Panc410, into living mice. For 30 days, they studied the effects of the two drugs and a control medicine, measuring the tumors twice a week. Both drugs shrunk tumors in Panc502 more than in Panc410, supporting the conclusion that the cell line technology had effectively predicted Panc502’s sensitivity to the two drugs.

The investigators have given one type of their genetically engineered mice to the Jackson Laboratory in Bar Harbor, Maine, a mouse genetics research facility, for breeding and distribution to other laboratories. They are looking to partner with a company to distribute two other types.

Study co-authors are from Johns Hopkins and Emory University School of Medicine. The work was supported by the National Institutes of Health, the Sol Goldman Pancreatic Cancer Research Center, the Stewart Trust Fund, the Lustgarten Foundation, the Mary Lou Wootton Pancreatic Pancreatic Cancer Research Fund, the Michael Rolfe Pancreatic Cancer Foundation and the HERA Foundation.

Maitra and Eshleman may receive royalty payments if the mice are licensed, and Eshleman is an advisory board member for Roche Molecular Diagnostics. These relationships have been disclosed and are under the management of the Johns Hopkins University School of Medicine Conflict of Interest Committee.

Source: Johns Hopkins University