Stem-like cells help glioblastoma defy treatment

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A slower-growing set of glioblastoma multiforme (GBM) cells appears to be the source of the brain cancer's recurrence after standard drug therapy is administered, new research reveals.

The most common primary malignant brain tumor, GBM is associated with a median survival of approximately 1 year. As Luis F. Parada, PhD, chairman of developmental biology at the University of Texas (UT) Southwestern Medical Center in Dallas, and colleagues noted in a letter published recently by the journal Nature, the poor prognosis is due to therapeutic resistance and recurrence of the tumor following surgical removal.

Now, Parada's group has identified a subset of endogenous glioma cells that are the source of new tumor cells following treatment with temozolomide (TMZ), the standard drug administered to arrest GBM growth. A genetically engineered mouse model demonstrated that these cells grow more slowly than others seen in the tumor, or remain at rest until needed. These resting tumor cells behave like stem cells, and are able to spur cancer recurrence following TMZ treatment by producing transient populations of highly proliferative cells.

“Current therapy targets fast-growing tumor cells but not those responsible for new tumors,” pointed out Parada in a statement issued by UT Southwestern Medical Center. “To the best of our knowledge, this is the first identification of a cancer stem-like cell in a spontaneously forming tumor inside a mammal.”

Once TMZ stopped tumor cell proliferation in the mice, the investigators observed a tumor regrowth cell hierarchy. A combination of ganciclovir and TMZ impeded redevelopment of the tumor.  

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