Drug development using one of these contaminated lines could be negatively impacted, according to the Journal of the National Cancer Institute.
A group of researchers report that three frequently used human esophageal adenocarcinoma cell lines actually come from other tumor types. Two of the cell lines have been used in 11 U.S. patents and more than 100 published studies, they say.
Details appear in a brief communication titled “Verification and Unmasking of Widely Used Human Esophageal Adenocarcinoma Cell Lines” and published online January 14 in the Journal of the National Cancer Institute.
The 13 established esophageal adenocarcinoma cell lines are important because of the limited availability of patient samples and animal models. To determine the authenticity of all the available cell lines, Winand N. M. Dinjens, Ph.D., department of pathology, Erasmus MC, University Medical Center in Rotterdam, The Netherlands, and colleagues used data from pathology archives and genotyping assays in collaboration with the primary investigators who established the cell lines.
Cell lines SEG-1, BIC-1, and SK-GT-5 were proven to be lung carcinoma, colorectal adenocarcinoma, and gastric fundus carcinoma, respectively. The remaining 10 cell lines were found to be aunthentic and will be placed in public repositories to promote future research.
“Experimental results based on these contaminated cell lines have led to ongoing clinical trials recruiting patients, to more than 100 scientific publications, and to at least three National Institutes of Health cancer research grants and 11 U.S. patents, which emphasizes the importance of our findings,” the investigators note in their JNCI communication. “Widespread use of contaminated cell lines threatens the development of treatment strategies for esophageal adenocarcinoma.”
The researchers also suggest that the clinical trial involving Barrett-related esophageal adenocarcinoma patients on Nexavar should be reconsidered since the wrong cell line was used; Bayer HealthCare and Onyx Pharmaceuticals market Nexavar for liver and kidney disease. They say there is now scant evidence for inhibition of the mitogen-activated protein kinase pathway by the drug in this cancer.
In an accompanying editorial, Robert Shoemaker, Ph.D., of the NCI, questions this suggestion, pointing out that tissue of origin may not be important for all research studies. “Given the knowledge that cancer is a heterogeneous disease, one might question the rationale for any therapeutic maneuver that is based on studies conducted on a single cell line.”
Dr. Shoemaker believes that a study conducted with the correct cell lines would probably provide the same rationale for Nexavar because alterations in mitogen-activated protein kinase pathways are common in many tumor types.