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Fueling Basic Discovery: NCI’s Cooperative Human Tissue Network

, by I. Lubensky, R. Chauqui, and J. Demchok

Credit: National Cancer Institute

Human biospecimens, as any cancer researcher will tell you, are a foundational resource in basic and clinical cancer research. And with the launch last year of President Obama’s Precision Medicine Initiative and his announcement in January about the launch of the National Cancer Moonshot Initiative, NCI-supported biospecimen programs have taken on renewed importance.

Quality biospecimens are critical to achieving the type of progress envisioned by both of these initiatives, whether it’s for conducting genomic analyses that will allow us to better understand cancer progression, discovering and validating biomarkers that can predict prognosis or response to therapy, or identifying new targets for therapy.

One of NCI’s longest running biospecimen programs is the Cooperative Human Tissue Network (CHTN). The CHTN meets a very specific need, serving as a resource mainly for basic discovery and early translational research.

Biomarker Discovery and Validation: A Challenging Pursuit

One area where the CHTN has played a pivotal role is in the early discovery of biomarkers. The biomarker  development pipeline begins with basic research, which produces much of the data about the molecular characteristics of disease, such as the expression of specific genes or proteins.

For example, if an investigator is trying to measure the presence of a protein using an antibody that binds to it, it’s important to validate that the antibody consistently binds to this protein and not to others. CHTN biospecimens, which include minimal information about the patients from which they came, are particularly useful for testing and validating such antibodies, which often form the foundation for biomarker assays.

Once a possible biomarker has been identified and the assay to measure it has been validated, then investigators can move to the next step and begin to assess its value using clinical samples that have detailed clinical data associated with them (e.g., the patient’s medical history, race, the treatments received, and the response to treatment).

It is challenging and complicated work, and often the result will be that the biomarker being studied does not meet the high bar demanded of these molecular signposts. Indeed, while many potential biomarkers have been discovered, only a few have proven to be clinically useful.

By providing high-quality biospecimens, the CHTN helps to ensure that biomarker discovery is producing more reliable results that can be reproduced by others. As a result, investigators can be more confident in their findings and ensure that they are advancing the most promising markers forward for further study—saving time and promoting more prudent use of available funding and resources.

Prospective Procurement: Meeting Researchers’ Needs

Although it shares many things in common with other biospecimen resources, perhaps the biggest difference between the CHTN and most other biospecimen resources is that it procures tissue prospectively, specifically at an investigator’s request. Prospective procurement means that sample preparation can be customized to the investigator’s needs, such as being fresh-frozen or fixed in special media.

Because requests are networked across the six CHTN partner institutions—five that procure adult specimens and one for pediatric specimens—most requests can be filled within several weeks.

In addition, certified pathologists test the samples to confirm histologically that the tissues are what the investigator requested. And, because it is an NCI-supported resource, the specimens are typically far more affordable than they would be from other sources.

In addition to biomarker discovery, the research made possible by the CHTN includes studies of basic tumor biology, the role of viruses in oncogenesis, and the regulation of gene expression, among others.

Valuable Resources for the Research Community

The CHTN, as we’ve said, is just one NCI-supported biospecimen resource. In addition to resources for early discovery, like the CHTN, the Institute also supports biorepositories from large NCI-funded studies and clinical trials with well-annotated samples that are ideal for later-stage translational research.

Quality biospecimens aren’t typically fodder for news stories that go viral. Rather, they represent some of the nuts and bolts of cancer research that are sometimes taken for granted. But quality biospecimens are a truly invaluable resource, and we encourage the cancer research community to take advantage of the CHTN and similar resources that NCI offers.

And we should never forget that biospecimens are only available thanks to the generosity of patients who, while dealing with their own disease, have agreed to make their biospecimens available in the hope that they can help somebody else.

Irina Lubensky, M.D., is chief of the Pathology Investigation and Resources Branch (PIRB) in NCI's Division of Cancer Treatment and Diagnosis. Rodrigo Chuaqui. M.D., and Joanne Demchok, M.S., are PIRB program directors.

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