Oncology

Blocking a Protein Halts Tumor Growth

Ovarian tumors seem to thrive in the presence of high levels of a protein known as TG2, short for tissue type transglutaminase. And the more advanced they are, the more TG2 there is. But blocking production of the protein in mice reverses the tumors' growth.

In fact, researchers at the University of Texas' M.D. Anderson Cancer Center found that ovarian tumors, even in their advanced stages, could be shrunk by an average of 86 percent if a biochemical known as siRNA (a tiny strand of ribonucleic acid incorporated in small fat particles injected intravenously) was used together with the chemotherapy drug docetaxel.

"Ovarian cancer often becomes resistant to chemotherapy and frequently spreads within the abdominal cavity," especially if the cancer tissue produces high levels of TG2, said Anil Sood, professor in M.D. Anderson's departments of Gynecologic Oncology and Cancer Biology, who led the research team. "Although TG2 seems to play a part in many steps involved in cancer growth, we had little information about its role in ovarian cancer until this study."

The study looked at 93 samples of ovarian cancer in mice. Researchers halted TG2 production using siRNA. Tumor growth stopped, and the malignancies shrank.

"We cannot predict if these results will be the same in humans, but in the future, we hope that the blocking of TG2 with siRNA may be an effective treatment in advanced ovarian cancer," said Sood.

He and his co-workers are planning to create an initial clinical trial using siRNA to block TG2 in ovarian and pancreatic cancers.
"TG2 does so many different things," said Kapil Mehta, a colleague of Sood's. "Normally, you would have to develop a small-molecule drug to block each function. Using siRNA is exciting, because it completely blocks everything TG2 does in one process."

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