The Keller Laboratory at cc-TDI: Tissue Banking

Wednesday, September 1, 2010

Tissue Banking - Demystified

A question sometimes asked is how research can be advanced, and contributing tissue to a tumor bank for research is a key element (money, yes, is nice... but high quality tissue from patients with tumors for which little is know is more valuable). And if it can be put in a gentle way, tumor tissue from the patients that researchers and clinicians so far have failed is the most valuable. That is, tissue from patients with relapses... even post-mortem biopsies from patients that have failed our best treatments.

How does one enroll to give tissue? In the case of soft tissue sarcomas, the Children's Oncology Group (COG) has had a tumor bank protocol called "D9902" open since March 1999. The consent form for this study is usually presented to families at the time a child is diagnosed and is being considered for a COG treatment study. Most people think of D9902 as a study for collecting tissue from the original untreated tumor, but... the protocol does already allow tissue to be collected from biopsies done at the time of relapse, as well as tissue taken after death (autopsies, partial autopsies and post-mortem biopsies). In practice, relapse samples rarely are collected (there are practical reasons not to subject children to extra procedures). Post-mortem samples are scarce... maybe none, with recent notable exceptions.

Where does the tissue go? well, a really good tumor bank! The COG contracts the Pediatric Cooperative Human Tissue Network (pCHTN) to store COG sample studies. Their Director is Dr. Nilsa C. Ramirez, and she and the Biopathology Center for the pCHTN are at the Nationwide Children's Hospital in Columbus, Ohio. Nilsa succeeds the late Dr. Stephen Qualman, who himself was taken by pancreatic cancer. Dr. Qualman was a leader in rhabdomyosarcoma pathology research, but Nilsa keeps this tradition in sarcomas strong, and she was recently joined by rhabdomyosarcoma researcher Dr. Peter Houghton who is building an exciting pediatric cancer research program at Nationwide.

What happens with the tissue? It gets used, hopefully! Dr. Stephen Skapek at the University of Chicago leads the Soft Tissue Sarcoma Biology subcommittee of the COG. Researchers send the pCHTN/COG applications to use the tissue. The applications are reviewed by Steve and others on his committee (such as myself). If the study looks promising, a few samples are sent. If the researcher shows promising results, many more samples can be sent. In fact, for the best studies we even consider, "emptying the bank". (important notes: the researchers only have de-identified samples... they won't know each patient's name. Also, statistical rigorousness is another important judging criteria for proposed studies).

How much does it cost? In theory, it shouldn't.... the tissue collection kits are meant to be a part of the existing COG D9902 protocol. However, there have been cutbacks in what the NIH/NCI gives COG for its studies. If there were a sudden 'flood' of samples, the pCHTN and I estimate it would cost $150 total (70 for the kit, 30 to ship the kit to the child's hospital, 50 to ship it back on dry ice). I've talked with a few foundations on whether they'd sponsor kits, and while we don't have any definite commitments, I think if the need arose we could find a way that patients wouldn't need to use their own money to contribute to research through the tumor bank.

I hope this helps with some of the questions arising lately. Feel free to comment on this blog or email me for more information.

Sincerely,
Charles

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You Can Participate in our Novel Therapeutics Studies !

One would like to think that tangibly better treatments for rhabdomyosarcoma, medulloblastoma and other childhood cancers can be found in a matter of years, instead of tens of years. Finding new treatments starts with research, perhaps even a new research approach to identifying effective new treatments. The Children's Cancer Therapy Development Institute focuses on finding molecules in childhood cancers that can be directly turned off or on by drugs so that the tumor stops growing. Behind our novel approach is the use of genetically-engineered mice. Our Pediatric Preclinical Testing Initiative uses mice modified from before birth so that at a certain age, and in a certain tissue, the same mutations found in a child’s cancer are activated in the mouse. These special mouse models of childhood cancer can be used to test a treatment to see whether the tumor growth and spread (metastasis) can be reversed. The specific aspect of these mice having normal immune systems is a real plus, too, because white blood cells play an important role in how tumors evolve and respond to therapy.

Our program is designed around community participation. Through the Children's Cancer Therapy Development Institute, you can contribute directly to this grass-roots initiative. Donations through small gifts or grants will assist in studying compounds that may be effective in treating such childhood cancers as alveolar rhabdomyosarcoma, embryonal rhabdomyosarcoma, or medulloblastoma (the alveolar rhabdomyosarcoma model was featured by Dr. Keller's long time collaborator and former mentor, 2007 Nobel laureate Mario Capecchi, in his Nobel Prize lecture {see 16 minutes onward}.)

For additional information regarding supporting this program please contact Charles Keller at charles@cc-tdi.org. Results obtained through these studies will be shared with the National Cancer Institute’s Cancer Therapy Evaluation Program, as well as the Children’s Oncology Group, which designs clinical trials for childhood cancer.