656 | CANCER DISCOVERY�AUGUST 2012 www.aacrjournals.org
NEWS IN BRIEF
Cell Lines Often Misidentified
Christopher Korch, PhD, doesn’t like being the bearer of bad news.
The director of the University of Colorado Cancer Center’s DNA Sequencing and Analysis Service recently analyzed a cell line that a researcher thought was endometrial cancer only to discover that it was actu-ally breast cancer. The news forced the researcher to halt publication of a study in which he had used the misidentifi ed cells. “It’s hard to tell someone that their conclusions may be fl awed and that they’ve lost 6 months’, a year’s, or a decade’s worth of work,” says Korch.
Unfortunately, such conversa-tions aren’t rare, says Korch. He and his colleagues recently published a study in Gynecologic Oncology that used DNA profi ling to analyze dozens of ovarian and endometrial cell lines collected from multiple institutions in the United States, Europe, and Japan. They found signifi cant rates of misidentifi cation, contamination, and redundancy among the samples.
Among 51 samples purportedly from ovarian cancer cell lines, the researchers identifi ed 8 as existing breast cancer, teratocarcinoma, or cervical cancer cell lines; 10 were redundant cell lines. Two supposedly normal endometrial cell lines were genotyped and found to be HeLa cervical carcinoma cells and MCF-7 breast cancer cells.
The new study adds to evidence compiled over several years showing that 18% to 50% of cell lines used in biomedical research, including cancer research, are misidentifi ed, contami-nated, or redundant.
Samples that are mislabeled and then shared aren’t the only cause of identity problems. Equipment could be improperly sterilized or two research-ers could be working with different cultures in the same hood, explains Korch. Also, cells can travel in aerosols, landing where they shouldn’t, and survive. “HeLa grows well and can out-compete if they get into the culture of a slow-grower,” he says.
The American Type Culture Col-lection, a nonprofi t biologic resource center based in Manassas, VA, released
PEOPLE
Howard Ozer, MD, PhD, known for his research on leuke-mias and lympho-mas, was appointed director of the University of Illinois Cancer Center
(UICC) in Chicago in June. He had been serving as interim director since the January 2011 death of the institution’s previous leader, Gary Kruh, MD, PhD.
Among other responsibilities, Ozer will oversee the UICC application to become a National Cancer Institute–designated cancer center.
Sir Mark Walport, PhD, MB BChir, director of the Wellcome Trust in the United Kingdom (UK), has been appointed as the UK Government Chief
Scientific Adviser, beginning in April 2013. Succeeding Sir John Beddington, he will help ensure that scientific knowledge informs policy decisions. Walport has led the Wellcome Trust, a global charity dedicated to funding biomedical research, since 2003.
John C. Reed, MD, PhD, chief executive officer of Sanford-Burnham Medical Research Institute in La Jolla, CA, was named editor-in-chief of Molecular
Cancer Therapeutics, effective August 1. He replaces Daniel Von Hoff, MD, the journal’s founding editor.
Reed earned his medical and doctoral degrees from the University of Pennsylvania School of Medicine in Philadelphia, where he also completed his clinical postdoctoral training. His research focuses on mechanisms that regulate apoptosis and how defects in apoptosis contribute to disease.
The recipient of numerous awards and honors, Reed has served on the editorial boards of several journals, including Cancer Research and Clinical Cancer Research.
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voluntary guidelines in January calling for the routine authentication of cell lines with short tandem repeat (STR) profi ling. Widely available, STR profi l-ing takes about a week and costs $100 to $200 per sample.
“It’s the equivalent of about 20 lattes to profi le a cell line and know whether what you have is what you want,” says Korch. “Is that too much to spend? Well, I’d rather be sure.” ■
NCATS–Industry Project Gains Backers
An effort by the NIH National Center for Advancing Translational Sciences (NCATS) to connect aca-demic researchers with industry to revive drugs that passed safety testing but failed for their initial treatment indications has signed on 5 additional pharmaceutical companies.
Early-adopters AstraZeneca, Eli Lilly, and Pfi zer, who backed the Discover-ing New Therapeutic Uses for Existing Molecules program at its launch in May, are being joined by Abbott, Bristol-Meyers Squibb, GlaxoSmith-Kline, Janssen Pharmaceutical Research and Development, and Sanofi .
In fi scal year 2013, the program will provide up to $20 million to fund 2- to 3-year cooperative research grants that propose to investigate new therapeutic uses for any of the 58 compounds pro-vided by the corporate partners.
The initiative “provides the oppor-tunity to tap into the collective brain power of scientists across the United States and match a great scientifi c idea with the right industry compound,” says program director Christine Colvis, PhD, of NCATS.
In addition, the pilot program’s template agreements for intellectual property rights “will signifi cantly reduce the amount of time it takes for each of the partners to negotiate the terms,” says Colvis.
For corporate partners looking to take advantage of external research tal-ent, the program makes perfect sense. “We’re a very small percentage of the total knowledge base,” says Donald Frail, PhD, vice president of Science New Opportunities at AstraZeneca Innovative Medicines in Waltham,
MA. “It’s been a very intentional strat-egy by AstraZeneca to implement open innovation paradigms and tap into that expanded knowledge.”
Six months ago, AstraZeneca joined a similar partnership program with the Medical Research Council in the United Kingdom. “We’re at the stage of col-laborating on full proposals now and we’re excited about that,” says Frail.
Additional NIH-funded efforts to re-engineer the drug development pipeline to encourage earlier and more extensive collaborations are likely, according to Colvis. ■
Gene Silencing in an Origami Package
Potentially, therapeutic RNA interference can knock out essential functions in tumors. The trouble is getting small interfering RNA (siRNA) to cancer cells, and only cancer cells, without causing an immune reac-tion. Now researchers have reported on using “DNA origami” to create a siRNA- carrying nanoparticle that shows promise in initial mouse studies.
Investigators at Massachusetts Institute of Technology (MIT), Harvard Medical School, and Alnylam Pharma-ceuticals (Cambridge, MA), who devel-oped the particles, say the design control afforded by the DNA-folding technique may lead to greater consistency and safety in therapeutic siRNA delivery.
The gene-silencing particle is a pyramid of DNA decorated with 6 siRNA strands, each of which carries
a tumor-targeting folate molecule at its tip. This structure is dictated by the sequence of the DNA and RNA strands themselves. When mixed together in the right order, they will self-assemble into a 30-nm spiky pyramid shape.
Daniel Anderson, PhD, an associate professor of chemical engineering at MIT who led the work, says the origami design method enabled them to fi nely control the size of the nanoparticles and the exact number and location of the folate molecules. This level of con-trol isn’t possible with other nanoparti-cle drug carriers such as liposomes.
After confi rming that particles car-rying luciferase-gene-silencing siRNA decreased expression of luciferase in HeLa cells in vitro, the researchers went on to test the particles in vivo. They labeled the nanoparticles with a con-trast agent and injected them in mice with human xenograft KB tumors.
The researchers then tracked the particles for 24 hours with computed tomography and fl uorescence imaging. The origami particles accumulated in the kidney and the tumor, but not in other major organs. The particles also circulated in the blood for about 24 minutes, 4 times longer than naked siRNA. “They take several trips around the body,” says Anderson.
To determine whether there was gene silencing in the mice, they did another set of studies in mice whose tumors expressed luciferase, whose expression was targeted by the siRNA particle. Two days after injection, imaging showed their tumors were 60% less bright. Blood samples showed no signifi cant increase in IFN-α immune response.
Accumulation of siRNA-carrying nanoparticles in tumors has been demonstrated in mouse studies and even in human studies before, notes Peter Beal, PhD, professor of chem-istry at the University of California, Davis. What sets this work apart is the ability to precisely control the posi-tion and density of the ligands using the origami design method. “This may lead to novel interactions with specifi c cell-surface receptors that may lead to more precise targeting, which would allow for lower doses and could increase safety,” Beal says. ■
For more news on cancer research, visit Cancer Discovery online at http://CDnews.aacrjournals.org.
• Roche is shutting down its Nutley, NJ, campus and consolidating oncology, virology, metabolism, and neuroscience research and development at existing sites in Germany and Switzerland. About 1,000 U.S. employees will be laid off. Roche said the move does not affect its Genentech subsidiary.
• By a margin of less than 1%, California voters turned thumbs down on a height-ened cigarette tax, the proceeds of which would have gone to cancer research, diagnosis, and prevention efforts.
• The U.S. Senate Appropriations Committee approved a spending bill that would give a $100-million boost for the NIH and a $13-million increase for the National Cancer Institute (NCI) for fiscal year 2013. Final appropriations are not expected to be set until after the November federal election.
• Worldwide, the biotechnology industry achieved more than 10% revenue growth in 2011 for the first time since the start of the global financial crisis, according to Ernst & Young’s annual bio-tech report. Research and development spending increased 9%.
• The population of cancer survivors in the United States, now estimated at 13.7 million, will near 18 million by 2022, according to a report by the American Cancer Society.
• Six academic medical centers are joining in a consortium that will conduct clinical trials and research for patients with myelodysplastic syndrome (MDS). The MDS Clinical Research Consortium is a 5-year, $16-million privately funded initiative.
• The automatic federal budget cuts that will go into effect in January if Congress does not pass sufficient deficit-reduc-tion measures would affect every NIH program, director Francis Collins, PhD, told the House Energy and Commerce Subcommittee on Health. “We wouldn’t do it in a completely blind fashion like a haircut, but everybody’s hair would get cut—pretty significantly,” said Collins. “There would be a lot of people with very short hair.”
NOTED
Standard templates for memos of under-standing (MOU) and collaborative research agreements (CRA) are key ingredients in the Disc overing New Therapeutic Uses for Existing Molecules pilot program. The agreements aim to streamline partnerships and provide a road-map for handling intellectual property.
