To benefit research, tissue repositories must be accountable.
Mention “bank rescue” these days and most people cringe. But there’s another type of repository—human tissue banks for cancer research—that also need help and pose important implications if they can’t keep pace with scientific advances.
Studying stored tissues that have been offered for research by patients can provide answers to some of the most common questions asked by people who have cancer, such as, “Will this cancer come back?” and “How long do I have to live now that I have cancer?” and “What is the best drug to use in treating my cancer?”
New ideas and therapeutic strategies need to be validated, and often, that validation process depends on tissue and biorepository banks. Notable examples of successful efforts include the development of tests to determine a woman’s risk of recurrence after breast cancer surgery, the development of several new drugs that target specific cancer-causing genes and the ability to determine the chance of a patient’s tumor responding to a given therapy based on testing the tumor.
The biobanking field, despite some progress in recent years, is still playing catch-up with genomic and proteomic studies in the lab. Armed with powerful, cutting-edge techniques in this age of “personalized medicine,” researchers can analyze the genes and proteins in banked specimens for biomarkers that may signal the development of cancer in individual cells, offer clues about response to treatment and lead to new cancer tests or therapies. However, proper statistical analyses require large numbers of cases.
The challenges for biobanking are daunting. A partial list includes inconsistent collection, processing and storage of tissue, which can alter its molecular composition and skew experimental outcomes; shortages of high-quality tissue; outdated preservation techniques; the high cost of and inadequate funding for repositories; patients’ lack of awareness about tissue donation; and, for competitive and other reasons, institutions’ hoarding specimens they might otherwise share with researchers elsewhere.
“The way we’re doing things is just inadequate—maybe worse than inadequate,” says Carolyn Compton, MD, PhD, director of the Office of Biorepositories and Biospecimen Research at the National Cancer Institute (NCI) in Bethesda, Md.
Collectively, biobanks store tissue, such as tumor slices, blood, saliva, urine, DNA and other bodily materials in formalin-fixed, paraffin-embedded blocks or at very cold temperatures, or sometimes using both methods along with the related clinical, pathologic or molecular information. By law, medical facilities must retain tissue samples for a specified number of years (the number varies among states), which could prove useful if patients later seek a second opinion, their cancer recurs or a new genetic test becomes available.
Separate from that process, fully informed patients may also consent to donate some of their leftover cancerous tissue—stripped of identifying information—for research at no cost to them, with the understanding that they will probably never personally benefit or even learn if scientists actually use it. However, the tissue needs to be linked to clinical information about the patient, such as the pathology of the tumor and long-term outcome—including if and when the tumor recurred or the patient died of the disease. Research questions related to that data could be asked years from now when new analytic technology develops.
Part of the difficulty in bringing more rhyme and reason to the biobanking industry is its scattershot nature, aside from the fact that there’s no oversight by any federal regulatory agencies. Biobanks vary widely. They may be public or commercial enterprises. They are spread out among universities and cancer centers, as well as different types and sizes of hospitals, pathology labs, drug companies and other facilities, sometimes in multiple places within a single institution. They might focus only on a certain type of cancer, as does a bank founded in 2005 by the Multiple Myeloma Research Consortium at a cost of between $2 million and $3 million. And they range from a small freezer tucked in the back corner of a lab to a multimillion-dollar operation with state-of-the-art equipment. Consider this: More than 300 million biospecimens are stored in public and private repositories throughout the U.S.
It’s a scenario that can send researchers hunting for just the right specimens. “Hodge-podge milieu” is how Deborah Collyar in Danville, Calif., describes it.
Collyar, 53, who is president of PAIR: Patient Advocates In Research, a group that helps get results to patients more quickly, twice received diagnoses of breast cancer, in 1990 and 1995, and underwent surgery, chemotherapy and radiation. After the second recurrence, she decided to donate tissue blocks from both of her cancers to research, retrieving and carrying them herself from the Bay Area hospitals where she had received treatment to a breast cancer biorepository at the University of California, San Francisco. She had learned enough about cancer research by that point to understand the specimens’ potential value.
“I actually had to make that happen myself,” Collyar says. “Most people are not going to do that or know how to do that. I really didn’t know how either. I just kept asking questions.”
Michael Morse, MD, a clinician and associate professor of medicine at Duke Cancer Institute in Durham, N.C., who is studying vaccines that stimulate the immune system to attack cancer and who relies on dendritic cell specimens for his research, says patients rarely bring up the topic of tissue donation. When he broaches the subject, “most people are perfectly fine with that because they are not going to need another procedure done for it,” he says. “They also like the idea of helping future research.”
Although the gap between biobanking and advances in the lab may not be closing as quickly as some would like, there have been positive developments. For example, a fairly standard practice now in cancer-related clinical trials is to collect, store and study tissue from the participants, then maintain the specimens for future investigations by those researchers or by scientists elsewhere who demonstrate a need for them. Not having to gather and store tissue anew saves resources.
A recently completed study involving approximately 10,000 patients with newly diagnosed, early-stage estrogen- and progesterone-positive, node-negative breast cancer took that approach. The TAILORx (Trial Assigning IndividuaLized Options for Treatment [Rx]) study used the Oncotype DX Breast Cancer Assay to determine which participants would be more likely to benefit from chemotherapy, thus reducing such treatment in women who were not likely to benefit from it. The primary results will be available in 2015.
Those banked specimens “will allow us to address other clinically important questions—study other tests, other biomarkers—without having to repeat the entire trial,” says principal investigator Joseph Sparano, MD, an oncologist and professor at Albert Einstein College of Medicine and Einstein Cancer Center in New York.
Encouraging signs of progress at the national level include efforts to establish a central, public-private cancer tissue repository called the Cancer Human Bank (caHUB) and research on new ways to preserve tissue. The NCI offers best practices on the operational, technical, ethical, legal and other issues in biobanking while a research group has published guidelines to foster more thorough, accurate and standardized reporting in medical journals of how biospecimens have been handled so researchers are aware of circumstances that may negatively impact their own follow-up study results.
Original plans for the NCI-funded caHUB called for collection and storage of many high-quality tissue specimens and distribution to researchers beginning in 2015. However, the federal funding crunch has nixed that plan, at least for now. Instead, the NCI’s Office of Biorepositories and Biospecimen Research, where caHUB is based, will use $23.5 million in federal stimulus funds to expand research on standards for collecting, processing, storing and disseminating tissue specimens, says Jim Vaught, PhD, the office’s deputy director.
“We still think the original caHUB central repository concept is very valuable and plan to come back to it if possible,” he says.
Could advances in the science of tissue preservation also help narrow the distance between cancer labs’ rapid headway at the microscopic level and biobanks’ tissue quality problems? Allison Hubel, PhD, associate professor of mechanical engineering and a cryopreservation expert at the University of Minnesota’s Masonic Cancer Center in Minneapolis, thinks so. She and her colleagues are developing microfluidic devices that can remove preservation solutions from cells without causing molecular damage, which reduces quality. In addition, they are investigating synthesized as well as naturally occurring compounds that might work better than current, less-than-ideal preservatives.
As Hubel notes, researchers depend on the generosity of today’s cancer patients for tissues that may yield dividends sometime in the future. The big question is whether biobanks can do their full part to help make those payoffs a reality.
Consider this: More than 300 million biospecimens are stored in public and private respositories throughout the U.S.