New Thyroid Cancer Cell Lines Developed to Correct Appalling Error

Scientists at the Mayo Clinic have developed four pure new laboratory lines of cells from anaplastic thyroid cancer (ATC) tissue that will allow researchers all over the world to study the disease with confidence that the cells are unadulterated, a new paper reported.

The study also tested five different drugs on these cell lines and found that they all suppressed malignant growth by “turning on” a tumor-suppressor gene.
   
The cell-line work corrects a dismaying problem discovered a few years ago by Mayo Clinic scientists that up to half of the world’s laboratory ATC cell bank was actually comprised of either colon or melanoma cancer.
   
So the Mayo researchers set themselves on a course to create ATC cell lines that would be indisputably pure, clearly originating from specific patients with this rare and deadly disease. There are only about 600 new ATC cases a year in the United States; thyroid cancer itself is uncommon. ATC patients typically survive just four or five months, as was the case with Chief Justice William Rehnquist’s death in 2005.
   
The four new cell lines, each with different mutations that drive the cancer, were reported in the Journal of Clinical Endocrinology & Metabolism. Mayo will be sharing them with scientists internationally.

“Since cell lines are immortal and can live forever, they are critical to research, and a major issue is cell line contamination leading to misidentification and drawing incorrect conclusions for specific cancers,” said John Copland, the study’s co-principal author and a cancer biologist at the Mayo Clinic campus at Jacksonville, Fla. “We provide higher standards for characterizing new cell lines at the genomic and molecular level that can be traced back to the originating tumor tissue.”
   
The Mayo study details the molecular and genetic nuances that differentiate each of the new cell lines. ATC researchers around the world can now consult the Mayo data to determine the parentage and purity of a particular cell line.
Lab cell lines must be pure because it is this area—experiments in the laboratory—that constitutes the first step toward innovations in cancer therapy. “We want to test different drugs against each cell line in which specific pathways are activated to see the effects,” said endocrinologist Robert Smallridge, the other co-principal author. “Each of those different combinations of molecular abnormalities is going to generate a different set of potential targets that can be attacked through drug therapy.”
   
In Smallridge’s estimation, it will be only a few years before it will be possible to thoroughly analyze an individual patient’s ATC genetic abnormalities, and come up with drugs to fit his molecular profile. “No two tumors may match each other,” he said, “but by understanding through a systems biology approach the multiple pathways that are active in the cancer, and then using a combination of drugs that inhibit these pathways simultaneously, we will begin to make progress against this cancer.”
   
The other aspect of the study involved the testing of five different medications—from an approved cholesterol-lowering drug to experimental transferase inhibitors—on the new cell lines. The team found that each of these agents turned on a tumor inhibition gene called RhoB, producing growth reduction.

A Mayo team led by Copland had earlier ascertained that the RhoB gene was turned off in ATC cells, as is the case in several other malignancies. Smallridge is now conducting a phase I clinical trial testing a drug that can reactivate the RhoB tumor suppressor ability.


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