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The use of human biospecimens in cancer research
Christopher A. Moskaluk M.D., Ph.D.
University of Virginia
Cancers are made up of cells…..
Which are made up of various molecules…..
Understanding the molecular and cellular basis of why cancer cells behave differently from normal cells makes up most cancer research efforts
DNARNAproteinslipids
Types of biospecimens
Tissue• Cancer• Non-neoplastic
Biofluids• Blood• Urine
A major source of cells and the biomolecules that make up those cells
Can be a source of cells, but mostly a source of biomarkers (molecules made by cells)
Types of biomarkers
Screening• Am I at risk of developing
cancer?• Can I detect my cancer
early? Diagnostic
• Do I have cancer?• What type of cancer do I
have?
Predictive• Will my cancer respond to
this therapy?• What therapy will my cancer
respond best to? Prognostic
• How long do I have doc? Post-treatment surveillance
• Has my cancer come back?
How are biospecimens used in cancer research?
Discovery science• Making associations• Surveys of biological, chemical and physical
attributes using cancer biospecimens– What does cancer look like?– What are cancer cells made of?– How does all of this differ from normal cells?– What potential biomarkers are present in the sample?
• New aspect of discovery science (“-omics”)– Assay hundreds to millions of molecules at once
How are biospecimens used in cancer research?
Experimental science• Understand mechanism – how cancer works• Experimental method
– Frame a hypothesis– Create a model system– Manipulate variables while holding other parameters
constant to test the hypothesis
• Biospecimens are used to create model systems
Creating experimental model systems from cancer samples
Isolate living cancer cells,grow them in containers
Cell culture Xenografts
Isolate living cancer tissue,implant into special animals
How are biospecimens used in cancer research?
Correlational science -looking for specific features in cancer biospecimens:• Experimental science correlation
– Are features of cancer predicted by a model system present in the tumors or bodies of cancer patients?
• Clinical trial correlation– What features of the patients’ cancer predict response
to therapy?– What changes are occurring in the cancer due to the
therapy?
Issues in access to cancer biospecimens
In routine clinical practice, only materials left over from routine histologic examination of tissues usually are kept.
These tissues are dead and are molecularly-damaged from the processing, hence are useful only for a limited range of studies.
Paraffin block
Embed representative pieces in wax blocksFix in
formaldehyde
Histologic section
Cut thin sections onto glass slides for microscopic examination
Thrown away after a few weeks Kept for years
Issues in access to cancer biospecimens
Obtaining fresh or flash-frozen tissue samples requires EXPENSIVE infrastructure not found in most non-academic clinical centers.
Blood and other fluid biospecimens are not routinely stored in routine clinical practice and again require specialized infrastructure to obtain and store
Issues in access to cancer biospecimens
Both the banking and use of biospecimens and annotated medical data fall under Federal Law concerning Human Subjects Research and Personal Health Information• Access to human subjects (and their biospecimens)
are under the purview of the Institutional Review Board of where the specimens were obtained
• Access to annotated clinical data is controlled by the HIPPA Privacy Board of where the specimens were obtained
Issues in access to cancer biospecimens
As a consequence of the expense and the regulatory complexity concerning human biospecimens, most biospecimens are used within the institutions that acquired them
Exceptions:• Multi-center research groups and cooperative clinical
trial groups often have specimen sharing agreements• A few national biospecimen resources
– CHTN, NDRI, DoD (PCBN, LCBRN)
• A few commercial sources, but VERY expensive
Conclusions
Human biospecimens are key to all stages and steps of cancer research• From basic science to clinical trials
Routine clinical practice does not reliably obtain such specimens for research• Investments in infrastructure required to obtain these
– Often neglected and underfunded
The numbers of, and access to, high-quality human cancer biospecimens remain issues