The zombies of cancer research

By Heather Buschman, Ph.D.
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The scientific symposium portion of San Diego’s annual Stem Cell Meeting on the Mesa fell on Halloween this year—good timing for a discussion about the dark side of stem cells: cancer stem cells.

Robert Wechsler-Reya, Ph.D., director of Sanford-Burnham’s Tumor Development Program, once said, “Current cancer therapies are like trying to kill a zombie by kicking it in the shins.”

Everyone knows you can only kill a zombie with a shot to the brains—anywhere else might slow it down temporarily, but only a very targeted hit to the head will get rid of it for good. (See the CDC’s Zombie Preparedness Guide.) So what Wechsler-Reya means is that the current methods for destroying or removing tumor cells are not aimed at what may, in some cases, be the actual “brains” of the problem—cancer stem cells.

Like other types of stem cells, cancer stem cells can self-renew, producing more cells. They also differentiate, specializing into other cell types. Those are very useful features when scientists are using stem cells to repair or replace diseased or damaged tissue (rebuilding heart muscle tissue after a heart attack, for example). However, cellular proliferation is also a hallmark of cancer.

In some cancers, stem cells may be the initial source of the problem, giving rise to tumors. They might also be the reason some tumors are resistant to standard cancer therapies such as chemotherapy or radiation therapy. What’s more, cancer stem cells can allow tumors to recur—even if the bulk of a tumor is removed, a few remaining cancer stem cells rise up to rebuild a new tumor. Like zombies, they are hard to get rid of.

Scientists are now trying to learn how stem cells turn to the dark side in cancer so that they can figure out how to better detect, prevent, and treat tumor growth—targeting the zombie’s brains, not just its shins.

Meet the four cancer stem cell (zombie)-fighting scientists who spoke at the 2012 Stem Cell Meeting on the Mesa:

Robert Wechsler-Reya, Ph.D., Sanford-Burnham Medical Research Institute
Wechsler-Reya chaired the session on cancer stem cells. He was the first to identify a new type of stem cell that, when functioning normally, develops into many different cell types in the cerebellum. But if this cell acquires certain mutations, it can also give rise to medulloblastoma, the most common malignant brain cancer in children. Wechsler-Reya’s team is now trying to better understand what drives medulloblastoma tumors and they are creating stem cell-based models that can be used to test new drugs that target the disease, especially the stem cells at its root. (Read more blog posts about Wechsler-Reya.)

Luke Lairson, Ph.D., The Scripps Research Institute
Lairson believes that small molecules can be used to influence stem cell behavior—telling them when to proliferate and when to differentiate, for example. These molecules could be further developed into new therapies that trigger tissue repair and regeneration. On the flipside, they could also be used to dampen cancer stem cells. At the meeting, Lairson spoke about his search for selective small-molecules that inhibit cancer stem cells in glioblastoma, the most common and lethal form of brain cancer.

Ben Spike, Ph.D., Salk Institute for Biological Studies
Spike’s talk centered on a mouse mammary gland model he’s using to better understand stem cell behavior and how cancer stem cells take input from the external environment. Spike is also interested in determining how stem cells differ from one another. In a paper he published a couple of years ago, Spike, his mentor, Geoffrey Wahl, Ph.D., and others suggested that cancer stem cells are not necessarily even part of the original tumor—they emerge later in the tumor’s development. They believe that genomic and epigenetic instability are responsible for this mix of different cell types in the tumor.

Catriona Jamieson, M.D., Ph.D., University of California, San Diego
As both a researcher and a physician, Jamieson provided a clinical perspective on cancer stem cells. She discovered cancer stem cells involved in the progression of chronic myelogenous leukemia (CML) to acute leukemia. She has also unraveled the molecular events that help CML cancer stem cells proliferate. Jamieson and her team are now developing methods to detect cancer stem cells in the body and testing them in clinical trials.

The Stem Cell Meeting on the Mesa was sponsored by the Sanford Consortium for Regenerative Medicine, Alliance for Regenerative Medicine, and California Institute for Regenerative Medicine.

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Heather Buschman, Ph.D.

Heather was a Sanford-Burnham Communications staff member.

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