Improvements in our understanding of disease have relied primarily on clinical trials backed by real-world evidence. Biological samples and large-scale datasets are key components in research today, particularly in relation to research aimed at understanding the prevalence of a disease and the discovery of new biomarkers for direct and molecularly targeted therapeutics.
Biobanks contain the programmed storage of human or biological specimens (such as tissues, organs, and cells) and associated data. These comprehensive repositories offer researchers the opportunity to obtain a greater understanding of complex diseases and human biology. Over time, biobanks have evolved from small-scale operations to larger, more sophisticated systems comprised of a diverse range of pathological materials for clinical research. Biomarker discovery and targeted drug development represent two of the advancements spurred by biobanks.
How Biobanks Are Fueling Translational Research and Drug Development
“Today’s greater understanding of tumor biology is changing the way cancer is defined, drugs are developed, and treatments are prescribed,” Zuanel Diaz, Ph.D., director of the protocol support laboratory and biospecimen research facility at the Miami Cancer Institute, tells GEN. “It has become evident that a patient’s response to treatment, with respect to both safety and efficacy, is highly dependent upon his or her molecular profile. Translational research and precision medicine initiatives developed throughout the globe have proven that the molecular analysis of advanced cancer and use of targeted therapy to counteract the effects of specific aberrations are associated with improved clinical outcomes.”
Translational research and precision medicines that are effective for addressing emerging oncology-related patient care paradigms rely on human biospecimens from cancer patients and healthy volunteers, Dr. Diaz adds. Using these biospecimens, researchers work to identify biomarkers and molecular signatures that are involved in specific stages of cancer development (that is, biomarkers involved in the regulation of tumor growth, metastasis, and drug resistance). In general, biospecimens require a high level of specificity to ensure effective research. These biomarkers, in turn, can be used, Dr. Diaz continues, to offer “confirmatory data generated on preclinical research, to facilitate the design of early-phase clinical trials, and to identify the patient population that would most likely benefit from experimental treatments.”
“In addition, our appreciation of the molecular diversity of cancer as a result of genomic partitioning is modulating the clinical research landscape,” Dr. Diaz emphasizes. “Correlative science studies are increasingly incorporated into early-phase trials to assess pharmacodynamics and monitor response or to detect therapeutic resistance and its underlying mechanisms. While technological advances support the necessary analyses of small biospecimens or profiling of circulating tumor markers (and patients are informed of the potential risk to participants associated with invasive procedures), these add an extra layer of complexity and demand sophisticated processing, handling, and tracking of biospecimens.”
At the Miami Cancer Institute, Dr. Diaz and colleagues have established the Biospecimen Repository Facility “as a scientifically justified, carefully designed, and efficiently implemented unit that collects, processes, and distributes highly specific and highly characterized biospecimens that are used in early therapeutic trials and that are stored for future research.” Contributions are comprised of biospecimens from patients with unique characteristics, medical histories, exposures, family histories, and social statuses. Its infrastructure, operational workflows, staffing, and support services models are highly specialized to serve the needs of the cancer center and the distinctive population in Florida and Latin America, Dr. Diaz explains.
The implications of biobanking also extend to the area of precision diagnostics as well as to the development of tailored therapies. “I like to think of biobanking as a key enabling technology and tool for precision medicine,” says Michael H.A. Roehrl, M.D., Ph.D., director of the Precision Pathology Biobanking Center at Memorial Sloan Kettering Cancer Center (MSKCC). “Although biobanking is central, it is only one of the pillars, with clinical trials being the main driving force behind how we do biobanking in order for us to perform next-generation precision research and diagnostics.”
At MSKCC, Dr. Roehrl and his team of research colleagues are focused on developing and utilizing new diagnostic technologies that require fewer samples to be analyzed. “Biobanking is often referred to as a repository, but it should really be a dynamic repository, one that is actively used to analyze tissues in each phase,” Dr. Roehrl comments. “Clinical trials have changed dramatically over the last five years. Analysis of human samples is now at the forefront of drug development, and we’re also interested in how we can integrate biobanking into companion diagnostic development.”
As for the importance of biobank specimens for advancing biological understanding and disease-related care, Dr. Roehrl adds that most specimens are relevant and important to research only to the extent they contribute to our understanding of outcome data, molecular characterization, and treatment response. His team at MSKCC has invested a great deal of time and resources into new IT technology “that has allowed us to mine data and create computable datasets and link these in real time to our biobank,” Dr. Roehrl says. “This has really been a game changer in the utilization and linkage of specimens with patient data.”
Recalling his talk at the 2018 Biobanking Congress held recently in Cleveland, OH, Dr. Roehrl discusses a point he made about biobanking in tailored drug development: “If you want to investigate a biomarker or develop a new companion diagnostic for a new drug, you need to have a lot more than a set of samples.” The combination of biobanking with drug development has only accelerated in recent years as biobanks help researchers elucidate complex disease etiology and improve the understanding of the molecular basis of disease, especially various disease subtypes. This sophisticated, biology-based disease classification is posited to facilitate the advancement of high-throughput strategies for targeted and possibly more effective therapies with fewer side effects.
The first step, however, requires a checklist of sorts, according to Dr. Roehrl: “You need to know how those patients fit, what mutations they may have, as well as how and when the patients were treated relative to when the samples were required.”
Biobanking and the Role of Organ Procurement Organizations
When asked how biobanking data can improve research initiatives as they relate to organ procurement, Julie R. Schneider Caldro, director of tissue services at Lifebanc, notes that these data “can help us collect and track data for organs and tissues recovered for research as well as identify and track information about specific disease processes from potential referrals.” Specific research initiatives have already brought forth breakthroughs and a greater understanding of how to achieve success in transplanting vascular composite allografts.
Lifebanc is a nonprofit Ohio-based organ procurement organization that facilitates organ, eye, and tissue donation services for transplant and research. According to Caldro, approximately 3% of deaths make way for organ donation to be possible, despite the fact that many people who do die are eligible for organ donation. Procurement of organ and tissue samples for biobank repositories is crucial for current and future research regarding several diseases, making increased awareness of organ donation an important aspect of routine clinical care.
“We utilize a medical advisory board that reviews all applications for research to determine if the study is aligned with our mission and the advancement of medicine,” Caldro explains with regard to Lifebanc’s biobanking processes. “The board also assesses the feasibility of the project and identifies if there would be any roadblocks to successful implementation. At Lifebanc, we have a research application that must be completed in advance. It collects very specific information about the research project, including scope of the project, number of specimens needed, and funding possibilities. The researcher is provided an opportunity to formally attend the meeting of the medical advisory board and present their research project in person so that the board has the opportunity to ask questions.”
The expectation, she notes, is that the process will be “a collaboration, and that the organ procurement organization will receive routine follow-up and updates on the research project to assess continuance for the coming year.”
At the Biobanking Congress, Caldro presented her talk, “Optimizing Research through Collaboration with Your Organ Procurement Organization,” providing insight into how organ procurement organizations can work with research teams to identify potential donors, specific diseases, and medical histories at time of death, as well as donation restrictions of organ and tissue samples. Common tissues that can be recovered for transplant and research purposes include pericardium, femoral vessels, saphenous veins, coneas, bone and connective tissues, and nerves.
Lifebanc partners with research teams to facilitate organ donations for the purposes of investigating the physiological mechanisms underlying coronary artery disease, diabetes, cancer, viral hepatitis, chronic kidney disease, cystic fibrosis, and chronic obstructive pulmonary disease, among other health issues. In addition, Caldro suggests that tissue samples from biobanks can improve the study of pharmaceuticals, resulting in new drug targets for various diseases, as well as refining knowledge regarding how changes in gene expression can contribute to highly prevalent diseases.
Advantages of Biobanks for Cancer Research
From an operational perspective, biobanks have specific criteria that must be met for ensuring optimal standards of stored biospecimens. Biobanks have also played an integral role in sharpening diagnostics as it relates to a diversity of disease states.
Jill S. Barnholtz-Sloan, Ph.D., professor and associate director for bioinformatics/translational informatics at the Case Western Reserve University School of Medicine, however, focuses some of her work in biobanks on how these specimens can have impact in real-world care, particularly in the care of brain cancer. “Our biobank is a brain tumor biobank,” Dr. Barnholtz-Sloan explains. “The upshot of it all is that we have leveraged our brain tumor biobank to make discoveries that are directly impacting patients, the most important of which is our involvement in The Cancer Genome Atlas project.”
The project, which became the biggest initiative from the International Cancer Genome Consortium, has incorporated research findings from at least 16 different nations and resulted in the discovery of approximately 10 million mutations associated with several different cancer types. Dr. Barnholtz-Sloan was closely involved in the project, leading a recruitment network of hospitals in Ohio whose work consequently resulted in changes to how brain tumors are diagnosed on a global scale.
“We utilized datasets to make discoveries and validate key molecular features of brain tumors that are directly associated with proper diagnoses,” Dr. Barnholtz-Sloan says. “That work involved leveraging our biobank and our network in Ohio and led to the World Health Organization modifying diagnostic codes for brain tumors to include the molecular features that we had found during our work on The Cancer Genome Atlas project.”
Dr. Barnholtz-Sloan expressed gratitude to her team and its work in the biobank, considering that this work will likely impact the lives of brain cancer patients, changing how their conditions are diagnosed and, potentially, managed.
To extend their reach, Dr. Barnholtz-Sloan and her colleagues are also working on structuring a method for assembling big health datasets so that researchers can ultimately have an impact on a large community. “At the Institute of Computational Biology in Cleveland, we’re trying to organize a large number of different big health datasets, some of that will include biobanking information, to try to have impact on the health of our Cleveland community,” Dr. Barnholtz-Sloan summarizes.
Part of the challenge with any biobank, she explains, is that biospecimens are only as good as the quantity and quality of clinical data you have on those patients. “If you have a biobank, and all you know is the diagnosis of the patient and the age of the patient, your options for doing something with that information are very limited,” Dr. Barnholtz-Sloan says. “But, if you also know what treatment the patient received, how long they survived, and/or whether or not they had other diseases, these factors make the biobank data more valuable. That’s why the integration of all these health datasets are important, because having more information actually empowers you to ask more comprehensive questions.”