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Treatment-induced growth factor causes cancer progression

In advanced cancer, anti-tumor therapies often work only partially or not at all, and tumors progress following treatment.

Vanderbilt-Ingram Cancer Center scientists have now linked a treatment-induced growth factor to the cancers future spread.

The team led by Carlos Arteaga, M.D., reports in the May issue of the Journal of Clinical Investigation that radiation and chemotherapy increase circulating levels of the growth factor TGF-beta, circulating cancer cells, and tumor metastases in a mouse model of metastatic breast cancer.

Blocking TGF-beta in the model prevented tumor metastases, suggesting that TGF-beta inhibitors may be clinically useful in combination with primary therapies.

Arteaga and colleagues had previously shown that a brief induction of TGF-beta in a transgenic mouse model of breast cancer dramatically accelerated metastasis.

Then they came across a few clinical studies showing that radiation and chemotherapy increase TGF-beta in patients or in experimental tumors.

"We wondered then if TGF-beta induced by anti-cancer therapies can serve as a survival signal for tumor cells, thus allowing them to withstand therapy and later recur," said Arteaga, professor of Medicine and Cancer Biology and director of the Vanderbilt-Ingram Breast Cancer Program.

This appears to be the case, he said. Radiation therapy and the chemotherapeutic agents doxorubicin and docetaxel all increased TGF-beta levels and accelerated metastasis, an effect that was blocked by neutralizing antibodies directed against TGF-beta.

Similar results not reported in this paper have been observed with small molecule inhibitors of the TGF-beta type I receptor kinase.

"We speculate, based on these observations, that this will occur in some patients," Arteaga said.

Patients who have treatment-induced increases in TGF-beta may not respond as well to the anti-cancer therapy as those who do n
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Contact: Heather Newman
heather.newman@vanderbilt.edu
615-936-7245
Vanderbilt University Medical Center
5-Apr-2007


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