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Brain Cancer
Cancer Center

Targeting An Especially Deadly Cancer

Scientists are learning more about glioblastoma multiforme, a particularly deadly cancer with a typical survival time of 15 months.

Researchers at the Salk Institute have discovered a key to how the tumor cells in glioblastoma multiforme proliferate so quickly —and ways to turn this engine of tumor growth into a target for cancer treatment.

“This is a disease for which there has been practically no improvement in treatment outcome for years,” said Inder Verma, professor in the Salk Institute’s Laboratory of Genetics and senior author of the paper published in the journal Science Advances. “It is clear that even if a surgeon removes 99.99 percent of a glioblastoma multiforme tumor, what is left behind will come back and grow into more tumor.”

To study how glioblastoma multiforme spreads, Verma’s team focused on a transcription factor called nuclear factor kB (or NF-kB). A transcription factor is a protein that binds to DNA and controls the fate of gene expression for a particular set of genes. Several known factors can trigger NF-kB activity in a cell, including ultraviolet and ionizing radiation, immune proteins (cytokines) and DNA damage.

In the case of glioblastoma multiforme, Verma and colleagues ran a battery of tests to show how overzealous NF-kB activity pushed the cancer cells to proliferate, and how stopping NF-kB slowed cancer growth and increased survival in mice.

“Our experiments confirmed that NF-kB is required for the cancer cell to proliferate,” said Dinorah Friedmann-Morvinski, first author of the paper and currently a researcher in the department of biochemistry and molecular biology at Tel Aviv University in Israel. “But now we have finally found a way to ameliorate the tumor to increase lifespan.”

Verma’s team started with a mouse model of glioblastoma multiforme and used genetic tools to manipulate cells into shutting down NF-kB activity in two ways. The team ramped up the presence of a protein called IkBaM, which inhibits NF-kB activity. They also eliminated an enzyme that increases NF-kB activity. With less NF-kB activity, tumor growth slowed and mice lived significantly longer then mice whose NF-kB activity was left alone. But while these genetic experiments demonstrated the role of NF-kB in glioblastoma multiforme, they aren’t a feasible treatment in humans.

“So we asked how could we manipulate the system using pharmacology rather than genetics,” says Verma.

Scientists have long suspected that one reason why glioblastoma multiforme comes back so quickly after surgery is the so-called tumor microenvironment. In other words, a tumor changes the environment of its surroundings (nearby tissues) to make it easier for cancer cells to thrive, Verma explains.

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