Food for Thought: Weekly Wrap-Up

Joachim Müller-Jung in Frankfurter Allgemeine Zeitung deals with the importance of high quality tissue for the development of personalized cancer therapies. He quotes Catheryn Compton, Director of the NCI’s Office of Biorepositories and Biospecimen Research (OBBR), as saying that billions of dollars have been wasted in the past because researchers developing biomarkers supposed to be predicitive of cancer and responses to therapies relied on tissue samples that were utterly useless:  tissue had been subject to careless handling and storage, and patient histories, data on origin and sampling procedure were missing, so that results were not reproducible. Müller-Jung features Hamburg-based Indivumed as the first and only ISO9001:2008 certified biobank in the world which offers cancer patient tissue and related technical and medical data derived in a standardized procedure accompanied by a detailed protocol.

Jef Akst in The Scientist reports on a new biomarker that can tell at early stages of liver and rare endocrine cancer whether a patient is likely to develop metastases. The biomarker, a protein called CPE-delta N, was able to predict the occurrence of metastases with greater than 90% accuracy, and using the associated RNA as a biomarker, the accuracy was even greater. Preliminary findings suggest it may also be applied to other cancer types.

In the same magazine, Megan Scudellari reports on findings that human cells reprogrammed into multipoint stem cells (so-called induced pluripotent stem cells, or iPS) have hotspots in their genome that are not completely re-programmed. The article raises the question whether iPS are really suited to replace embryonic stem cells.

Detecting volatile substances is the topic of several papers. In New Scientist, Jessica Hamzelou reports on attempts by various research groups to accelerate diagnosis in the operation theater by combining electrosurgery with NMR spectroscopy. The smoke emanating from the cut tissue is directed to a NMR spectrometer which analyses on the spot whether the surgeon is cutting healthy or cancer tissue.

Also in New ScientistArlene Weintraub reports on the Israeli start-up BioExplorers which claims that trained mice are better at detecting explosives than currently used devices and methods. As soon as the mice sniff traces of any of 8 explosives, they flee to a side chamber of their cage as if they are smelling a cat. Scientists from Colorado State University have taught tobacco and mouse-ear cress plants a similar trick – exposed to vapors from TNT, the plants change color. The trick is done by reengineering a certain receptor, reports Ferris Jabr. German Spiegel features a publication by Japanese scientists from Kyushu University who trained a dog to sniff out early-stage colon cancer with a success rate of 90%. The researchers now try to find out which chemicals the dog reacts to.

Ben Coxworth in Gizmag reports on blood clots made visible by nanoparticles. Each particle, developed by Dr. Dipanjan Pan at the Washington University School of Medicine  in St. Louis, Missouri, contains a million atoms of bismuth  and molecules binding to fibrin, a key component of blood clots, at the outside. Bismuth is a toxic heavy metal, which can be detected by a spectral CT scanner. In contrast to regular CT scanners, this new type of scanner is capable of displaying detailed objects or metal in color. Coxworth concludes that “not only could the technology be used to locate blood clots, but it could possibly even treat their cause – ruptures in artery walls. If the nanoparticles contained some sort of healing agent, then once they attached to the fibrin in a blood clot, they could set about sealing any weak spots.”

Food for Thought: Why tissue sample quality matters for personalized medicine

“We now have the technical ability to get the wrong answers with unprecedented speed.” Carolyn Compton, Director, Office of Biorepositories and Biospecimen Research

When the U.S. National Cancer Institute recently started its Cancer Genome Atlas initiative and asked biobanks all over the world for cancer biopsy samples, it was puzzled to find that the quality of the donated samples was so poor that the NCI was unable to meet the moderate target of collecting 1,500 biopsy samples per cancer. In a telling article in “Wired magazin”, Steve Silberman gives the example of a university biobank, which claimed to have more than 12,000 samples of glioblastoma in its collection. However, the initiative judged only 18 of those as good enough to use. After contacting biobanks on a global scale, the researchers did not even get to 500 glioblastoma samples of satisfactory quality and barely got to 500 in ovarian cancer, the 5th most common cancer in women. In lung cancer, the initiative was unable to start because it simply could not obtain the minimum number of biopsy samples of adequate quality. „However, all biobanks thought they were doing a superb job,“ resumed Carolyn Compton, director of NCI‘s Office of Biorepositories and Biospecimen Research OBBR and responsible for the biopsy sampling part.
The reason for the poor quality is simple: minutes after cutting tissue off from blood supply, cells start to react with massive changes in gene methylation patterns, gene expression and translation, proteome composition, enzymatic activities, surface protein patterns, etc. The changes affect hundreds of genes, and it is reality in many hospitals that the resected cancer tissue lies around for hours at room temperature in the operation theater before it is put in the freezer to get formalin-fixed a few days later.
Even more, the medication the patient has been given prior to or during operation (sedatives, anesthetics, etc.) has a profound impact on these parameters as well.
Therefore, very often it is impossible to judge whether the changes observed between individual patients is a result of their inherently different metabolisms/genetic makeup or a consequence of different sampling and handling of the biopsies and medications.
“We now have the technical ability to get the wrong answers with unprecedented speed,” Compton says. “If we put the wrong stuff into the front end of our analytical pipeline, we will not only lose the war on cancer, we’ll pollute the scientific literature with incorrect data that will take us a long time to sort out. This is a crisis that requires disruptive innovation.”
OBBR is now systematically looking into the problem and has chosen one company to perform the first systematic studies: Hamburg-based Indivumed GmbH. The company did pioneering research and devised standards for cancer biopsy samplings that are applied in a network of clinics Indivumed is collaborating with in the Hamburg and the Washington DC area. The company runs the only ISO-certified biobank in the world and is offering biospecimens, related patient data, and services including biomarker development for the purpose of developing personalized cancer therapies. By employing specially trained nurses, the company guarantees that each sample is frozen or fixed within 12 minutes, and each sample comes with a data package comprising several hundred data on the patient‘s medical history and life style. Further information about Indivumed, a client of akampion, can be found here.