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 DNA RNA proteins lipids

Types of biospecimens  Tissue CancerCancer Non-neoplasticNon-neoplastic  Biofluids BloodBlood UrineUrine 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?Am I at risk of developing cancer? Can I detect my cancer early?Can I detect my cancer early?  Diagnostic Do I have cancer?Do I have cancer? What type of cancer do I have?What type of cancer do I have?  Predictive Will my cancer respond to this therapy?Will my cancer respond to this therapy? What therapy will my cancer respond best to?What therapy will my cancer respond best to?  Prognostic How long do I have doc?How long do I have doc?  Post-treatment surveillance Has my cancer come back?Has my cancer come back?

Types of cancer research  Discovery science  Experimental science  Correlational science

How are biospecimens used in cancer research?  Discovery science Making associationsMaking associations Surveys of biological, chemical and physical attributes using cancer biospecimensSurveys 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”)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 worksUnderstand mechanism – how cancer works Experimental methodExperimental 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 systemsBiospecimens 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 correlationExperimental science correlation –Are features of cancer predicted by a model system present in the tumors or bodies of cancer patients? Clinical trial correlationClinical 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 blocks Fix 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 obtainedAccess 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 obtainedAccess 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 agreementsMulti-center research groups and cooperative clinical trial groups often have specimen sharing agreements A few national biospecimen resourcesA few national biospecimen resources –CHTN, NDRI, DoD (PCBN, LCBRN) A few commercial sources, but VERY expensiveA few commercial sources, but VERY expensive

Conclusions  Human biospecimens are key to all stages and steps of cancer research From basic science to clinical trialsFrom basic science to clinical trials  Routine clinical practice does not reliably obtain such specimens for research Investments in infrastructure required to obtain theseInvestments in infrastructure required to obtain these –Often neglected and underfunded  The numbers of, and access to, high-quality human cancer biospecimens remain issues