A new US study reports that a treatment-induced growth factor called TGF-beta helps contribute to the spread of advanced cancer.
Anti-tumor therapies work only partially or not at all in patients with advanced cancer, and tumors keep growing after treatment according to a research team at Vanderbilt-Ingram Cancer Center in Nashville, Tenn.
The research team, led by Carlos Arteaga, M.D., reports in the May issue of the Journal of Clinical Investigation that chemotherapy and radiation increase circulating levels of the growth factor TGF-beta, circulating cancer cells, and tumor metastases in a mouse model metastatic breast cancer.
The scientists also stated that blocking TGF-beta in mice prevented tumor metasases. This indicates that the us of TGF-beta inhibitors combined with primary cancer therapies may help patients.
The team had previously shown that a brief induction of TGF-beta in a mouse model of breast cancer can drastically raise the rate of metastasis.
They then noticed that a few clinical studied showed that chemotherapy and radiation treatment increase TGF-beta in patients or experimental tumors.
“We wondered … 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,” and this study shows that this appears to be the case, research team leader Dr. Carlos Arteaga, professor of medicine and cancer biology, and director of the Vanderbilt-Ingram Breast Cancer Program, said in a statement.
Radiation therapy and chemotherapeutic agents docetaxel and doxorubicin all increased TGF-beta levels as well as accelerated metastasis. This was blocked by neutralizing antibodies directed against TGF-beta.
Similar results 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.
Arteaga also said that several TGF-beta inhibitors are currently in clinical trials.
“It probably isn’t just TGF-beta that is having this effect. There are other growth factors and cytokines that have been reported to increase in response to radiation, chemotherapy and surgery, and some of these could also be tumor survival and prometastatic signals. TGF-beta may be just the tip of the iceberg,” he said.
The team is currently analyzing TGF-beta levels in the serum of patients with breast cancer who are being treated with neoadjuvant chemotherapy in order to shrink the tumor before surgery.