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Tumors for a cure

by Tom Walsh / Photography by William Foster

Cancer affects millions of people every day.

Yet no two cancer tumors are alike.

Each individual's genetic makeup is unique, and so is the biomolecular architecture of the cancerous tumors that will disrupt the lives of half of the men and a third of the women in America. That biological conundrum means that a one-size-fits-all approach to cancer therapies and cures is a dead end.

To confront that reality, The Jackson Laboratory has established a consortium with University of California Davis (UC Davis) Cancer Center in Sacramento and Swedish Hospital in Seattle. Cancer researchers have launched an ambitious effort to use living human tumor samples to devise and test cancer treatments.

"When you look at drug discovery, about 96 percent of all investigations of new drugs for cancer fail," says Ralph deVere White, M.B., B.Ch., B.A.O. (he obtained his medical degrees from Dublin University in Ireland), director of the UC Davis Cancer Center and a prominent urological oncologist and surgeon. "This contributes to the incredible expense of treating cancer and incredibly slow progress. What we need to try to quicken this up are better tumor models."

The biomedical research community needs a common, readily accessible tumor resource to support cancer drug development efforts.

Cancer researchers at UC Davis and at Swedish Hospital are working to enlarge the Human Tumor Consortium's inventory of human tumor samples. The "tumor library," as it is known, is located at The Jackson Laboratory—West in Sacramento, the California facility of the Bar Harbor, Maine-based Laboratory.

While tumor cells can be grown outside of the body in laboratory incubators, such cultured cells lose many of their original characteristics, and the growth environment is far from ideal. Working with a type of mouse recently developed at The Jackson Laboratory that can accept human tissue, deVere White, his UC Davis colleagues and scientists at JAX—West are working on developing a better resource for cancer research.

Pea-sized fragments of tumors derived from UC Davis Cancer Center patients undergoing surgical bladder removal are implanted in multiple mice at JAX—West within an hour after surgery. The human tumor tissue will then be used in a co-clinical trial strategy for brain, bladder, lung and other cancer therapies.

"By being able to engraft these human tissues we can, for the first time ever, study a tumor intact with the cells and factors that help propagate this tumor in a human being," says Neal Goodwin, the JAX Cancer Services program director. "It's the most human-like method to preserve and study these tumors, and to treat them with chemotherapy agents to find promising new cancer therapies."

deVere White believes this new approach to growing human cancer tissues yields far more useful insights than what can be derived from cultured cells grown in a lab.

"When you take cells out of a patient and you put them in tissue culture, you normally have to put in so many factors that help them grow that, if they do grow, they no longer resemble what was in the patient," he says. "We would hope to be able to take the tumors that grow in the mice and put them into tissue culture. If this works, it means the tumors that grow in the mouse really do look like the tumors that came from the patient. Our early indications are that we are very faithfully reproducing them, and that's very exciting."

Beyond bladder cancer tumor samples, the JAX—West tumor library now includes more than 100 cell samples harvested from human cancers of the lung, prostate, colon, kidney, pancreas, brain and breast, as well as tissues from cancer patients with lymphoma and sarcoma. Once the tumor grows in the mouse, it is removed, subdivided, placed into a new set of mice and allowed to grow again. Goodwin says this process will yield enough specific and identical tumor material to test cancer drugs in thousands of laboratory mice.

The Human Tumor Consortium plans to collect as many as 60 tumors from each of the major tumor types by 2014 and is recruiting collaborating cancer research institutions to meet that goal. "The pace of tumor acquisition and the limited amount of tumor tissue available for study present serious limitations to the biomedical research community." Goodwin says. "At JAX—West we're in the process of creating a publicly available library of patientderived tumors."

Beyond providing the state-of-the-art facilities in Sacramento that are required to archive and to maintain the tumor library, The Jackson Laboratory has made a substantial financial commitment to the project since it was launched in 2009.

"We'll also provide the databases needed to manage the tumor archive and the infrastructure needed to process orders for tumor fragments and for drug testing services," says Goodwin. "We believe that this resource should be made available to cancer researchers. We want these tumors to be readily accessible to both the academic and for-profit research communities."

The tumors will be characterized based on their individual gene expression patterns and other identifying traits. "Eventually, clinicians might be able to use this information to predict outcomes and identify the best treatment regimen for each person's cancer," says Goodwin, "enabling doctors to turn the tide of the battle against cancer one healthy patient at a time."

We all want to participate in something that may be a game-changer.

"The biomedical research community needs a common, readily accessible tumor resource to support cancer drug development efforts. No single cancer center has a patient population broad enough to meet this need. The tumor library will support large-scale basic and preclinical research studies, which should speed discovery and development of new cancer drugs."

deVere White thinks that The Jackson Laboratory is the ideal hub for this ambitious new endeavor.

"We have the patient population, and The Jackson Laboratory has this unique mouse. But, much more important than the mouse is their unique expertise in developing mice."

But while the mouse is the tool, deVere White is focused on what the new approach might mean for cancer patients. And he anticipates a remarkable end result.

"We all want to participate in something that may be a game-changer," he says. "Most of our life is spent making incremental advances, which are very important as you can't have everyone just swinging for the fences. But, inherently, just to do this, there is no way to do it except to swing for the fences. As long as we are sensible in looking at the milestones, it's nearly impossible that we will come out of this without something that will improve cancer research and cancer care. It's just a matter of whether we go all the way and really have a paradigmshifting chance. What more can you ask for?"