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Chemoradioimmunotherapy as Future Treatment for Advanced Breast Cancer

A successful, and novel, technique to kill metastatic breast cancer cells by circumventing their chemo- and radioresistant mechanisms was by presented by Dr. John Giannios, Head of Radiotherapeutic Cancer Research at the IASO Hospital, Athens, Greece at the 18th Annual Meeting of the European Association of Cancer Research.

Advanced breast cancer, with metastases to lung and bone, has a poor prognosis and current treatment protocols for this stage of disease generally result in survival periods of less than two years. One of the reasons for this poor prognosis is that metastatic cancer cells are less responsive to treatment than primary tumor cells.

This is partly caused by the fact that the normal cell death process (apoptosis) is repressed by the overexpression of oncogenes such as bcl-2, HER-2, Raf-1 and cdc25c (these oncogenes are expressed more strongly in metastatic tumor cells), which means that the cells fail to die following treatment with chemotherapy drugs and radiation therapy.

The experimental treatment, termed 'chemoradioimmunotherapy', combined chemotherapy, radiation therapy and immunotherapy in one. The chemotherapy component consisted of vinorelbine-tartrate (a cytotoxic drug used in the treatment of breast (and other) cancers), the radiotherapy component was provided through the addition of high energy radioisotopes, whilst the immunotherapy aspect was achieved by attaching an antibody specific to HER-2 to those radioisotopes, as well as through the inclusion of a separate 21-nucleotide double stranded siRNA ('small interfering RNA') generated against DNMT1.

It was hoped that the novel treatment regime would effectively target the tumor cells by blocking the genetic mechanisms that protect the cells from conventional treatment thereby allowing the chemotherapy and radiation therapy components to exert their cytotoxic effects.

In fact, by 24 hours post-treatment there was clear evidence that the treated tumor cells were undergoing significantly greater apoptosis (cell death) than the untreated controls.

"These results open the possibility of combining targeted immunotherapy with chemotherapy and radiation therapy to successfully kill metastatic tumor cells", said Giannios. "Our next step will be to develop the treatment in patients, and on a bigger scale, in a Phase I clinical trial."

SOURCES:
18th Annual Meeting of the European Association of Cancer Research, July 6, 2004, Athens, Greece
Federation of European Cancer Societies (http://www.fecs.be)



 




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