"Long before it's in the papers"
January 14, 2010

RETURN TO THE WORLD SCIENCE HOME PAGE

Report: cancer studies used wrong cells

Jan. 14, 2010
Courtesy Journal of the
National Cancer Institute
and World Science staff

More than 100 pub­lished stud­ies and two clin­i­cal tri­als in­volv­ing esoph­a­ge­al can­cer are based partly or wholly on re­search that mis­taken­ly used cells from other types of can­cer, a re­port claims.

Its au­thors sug­gest the find­ings may re­flect a wid­er prob­lem in can­cer re­search—that cells thought to be from one type of can­cer ac­tu­ally come from a to­tally dif­fer­ent type.

The re­port, by Winand N.M. Din­jens of Eras­mus Univers­ity Med­i­cal Cen­ter in the Neth­er­lands and col­leagues, ap­pears Jan. 14 on­line in the Jour­nal of the Na­t­ional Can­cer In­sti­tute. In the case of esoph­a­ge­al can­cer, the au­thors said, their in­ves­ti­ga­t­ion re­vealed that three often-used cell lin­eages were ac­tu­ally from co­lon, lung or gas­tric can­cer. The lin­eages were thought to be tu­mor cells from esoph­a­ge­al ad­e­no­car­ci­noma, one of two main types of esoph­a­ge­al can­cer.

More gen­er­al­ly, among lin­eages of tu­mor cells used in bas­ic can­cer re­search, “it has been es­ti­mat­ed that up to one-third… have an or­i­gin oth­er than that sup­posed,” they wrote. The re­port appears Jan. 14 in the Jour­nal of the Na­t­ional Can­cer In­sti­tute. “In the past, the sci­en­tif­ic com­mun­ity has rec­og­nized this prob­lem, but de­ci­sive ac­tion has not been tak­en,” they con­tin­ued. The re­port at­trib­ut­ed the mis­takes to “cross-contamina­t­ion be­tween cell lines and mis­la­bel­ing of cul­tures.”

“Widespread use of con­tam­i­nated cell lines threat­ens the de­vel­op­ment of treat­ment strate­gies for [e­soph­a­ge­al ad­e­no­car­ci­noma],” the au­thors wrote. They also noted that 11 patents to date are based on the erro­neous stu­dies. 

Two clin­i­cal tri­als in the Un­ited States are partly or wholly thrown in­to ques­tion by the find­ings, they added. 

The first, a Univers­ity of Chi­ca­go trial en­ti­tled The Ef­fects of So­rafenib on Mo­lec­u­lar Bar­ret­t’s Esoph­a­gus Can­cer, is cur­rently re­cruit­ing pa­tients, with a goal of ob­tain­ing 15 vol­un­teers. The sec­ond seeks to en­roll 85 pa­tients, but oth­er types of can­cer are al­so in­clud­ed. The stu­dy, spon­sored by Geron Corp., is en­ti­tled Safe­ty and Dose Study of GRN163L Ad­min­is­tered to Pa­tients With Re­frac­to­ry or Re­lapsed Sol­id Tu­mor Ma­lig­nan­cies.

The first of these tri­als should be “re­con­sid­ered,” Din­jens and col­leagues wrote.

But Rob­ert Shoe­maker, a sci­ent­ist at the Na­t­ional Can­cer In­sti­tute at Fred­er­ick, Md., dis­a­greed. He said that the ra­t­ionale be­hind the Univers­ity of Chi­ca­go study is based on a chem­i­cal path­way com­mon to many tu­mor types. Thus it does­n’t nec­es­sarily de­pend on a spe­cif­ic type of can­cer cell hav­ing been used in the or­i­ginal stud­ies.

More­o­ver, be­cause even a sin­gle tu­mor con­tains dif­fer­ent cell types, “one might ques­tion the ra­t­ionale for any ther­a­peu­tic ma­neu­ver that is based on stud­ies con­ducted on a sin­gle cell line,” he wrote, in an ed­i­to­ri­al accompan­ying Din­jens’ re­port in the jour­nal.

* * *

More than 100 published studies, two clinical trials and 11 patents involving esophageal cancer are based partly or wholly on research that used the wrong cells, a report claims. The authors suggest the findings may reflect a wider problem in cancer research—that cells thought to be from one type of cancer actually come from a totally different type. The report, by Winand N.M. Dinjens of Erasmus University Medical Center in the Netherlands and colleagues, appears Jan. 14 online in the Journal of the National Cancer Institute. In the case of esophageal cancer, the authors said, their investigation revealed that three often-used cell lineages were actually from colon, lung or gastric cancer. The lineages were thought to be tumor cells from esophageal adenocarcinoma, one of two main types of esophageal cancer. More generally, among lineages of tumor cells used in basic cancer research, “it has been estimated that up to one-third… have an origin other than that supposed,” they wrote, reporting their findings Jan. 14 in the Journal of the National Cancer Institute. “In the past, the scientific community has recognized this problem, but decisive action has not been taken,” they continued. The report attributed the mistakes to “cross-contamination between cell lines and mislabeling of cultures.” “Widespread use of contaminated cell lines threatens the development of treatment strategies for [esophageal adenocarcinoma],” the authors wrote. Two clinical trials in the United States are partly or wholly thrown into question by the findings, they added. The first, a University of Chicago study entitled The Effects of Sorafenib on Molecular Barrett’s Esophagus Cancer, is currently recruiting patients, with a goal of obtaining 15 volunteers. The second seeks to enroll 85 patients, but other types of cancer are also included. The study, sponsored by Geron Corp., is entitled Safety and Dose Study of GRN163L Administered to Patients With Refractory or Relapsed Solid Tumor Malignancies. The first of these trials in particular should be “reconsidered,” Dinjens and colleagues wrote. But Robert Shoemaker, a scientist at the National Cancer Institute at Frederick, Md., disagreed. He said that the rationale behind the University of Chicago study is based on a chemical pathway common to many tumor types. Thus it doesn’t necessarily depend on a specific type of cancer cell having been used in the original studies. Moreover, because even a single tumor contains different cell types, “one might question the rationale for any therapeutic maneuver that is based on studies conducted on a single cell line,” he wrote, in an editorial accompanying the Dinjens’ report in the journal.