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Solid tumor cells not killed by radiation and chemotherapy become stronger
Date:6/9/2008

DURHAM, N.C. Because of the way solid tumors adapt the body's machinery to bring themselves more oxygen, chemotherapy and radiation may actually make these tumors stronger.

"In a sense, these therapies can make the tumor healthier," said Mark W. Dewhirst, D.V.M., Ph.D., professor of radiation oncology at Duke University Medical Center. "Unless the treatment is very effective in killing many if not most tumor cells, you are shooting yourself in the foot."

Dewhirst and colleagues Yiting Cao, M.D., Ph.D., of Duke Pathology, and Benjamin Moeller, M.D., Ph.D. have introduced this counter-intuitive idea at recent conferences and in a review article featured in the June issue of Nature Reviews Cancer.

Radiation and chemotherapy do kill most solid tumor cells, but in the cells that survive, the therapies drive an increase in a regulatory factor called HIF1 (hypoxia-inducible factor 1), which cells use to get the oxygen they need by increasing blood vessel growth into the tumor. Solid tumors generally have low supplies of oxygen, Dewhirst explained and HIF1 helps them get the oxygen they need.

The review article concludes that blocking HIF1 would provide a clear mechanism for killing solid-tumor cells, particularly cells that are proving resistant to radiation or chemotherapy treatments.

As a part of this work, Dewhirst's team has been studying the phenomenon of rising and falling oxygen levels in tumors, called cycling hypoxia. Oxygen levels have been found to naturally cycle up and down in individual blood vessels as well as large tumor regions. This instability in the tumor's oxygen levels can increase HIF-1 production and cause radiation therapy to fail, Dewhirst said.

"It is my opinion that the whole tumor grows more aggressively because of this pulsation of oxygen at low levels," Dewhirst said. "Most people thought cycling hypoxia was caused by temporary stoppage of blood flow in single blood vessel in
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Contact: Mary Jane Gore
mary.gore@duke.edu
919-660-1309
Duke University Medical Center
Source:Eurekalert

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