HER2 Support Group Forums - View Single Post - are her2+ (and/or EGFR+) tumors more radioresistant (ie radiation therapy doesn't

Lani · 10-31-2006, 05:13 PM

These data raise concerns about increased radioresistance in tumors that overexpress HER-1 and HER-2. Irradiation may activate the EGFR signaling pathway as part of a cellular protective response, and inhibitors may abrogate this response. For example, overexpression of HER-2 in MCF-7 breast cancer cell lines enhanced the activation of the transcription factor, NF-B, induced in response to radiation (9). Trastuzumab both inhibited NF-B and increased the cells' radiosensitivity. In a group of six breast cancer cell lines, high levels of HER-2 expression correlated with radioresistance (11). Treatment with trastuzumab enhanced radiosensitization, depending on the level of HER-2 expression, by reducing phosphorylation of downstream molecules Akt and MAPK. A study in breast cancer cell lines that endogenously overexpress HER-1 or HER-2 or which were transfected with HER-2 were treated with an EGFR/HER-2 inhibitor prior to irradiation (8). The drug inhibited EGFR tyrosine phosphorylation in all cell lines and increased radiosensitivity in some.

A study using a novel small molecule EGFR inhibitor, CI-1033, in irradiated human breast cancer cell lines demonstrated a 23-fold increase in growth inhibition compared to radiation alone (23). Similar results have been seen in cells overexpressing HER-2 and treated with monoclonal antibody (13), an anti-erbB-2 single-chain antibody (10), and in various cell models using EGFR inhibitors, such as ZD1839 (Iressa) (11). Clinical studies of EGFR manipulation in breast cancer are limited, although there are several trials using EGFR inhibitors in the treatment of head and neck, and lung cancers (24–27).

10-31-2006, 05:13 PM	#3
Lani Senior Member Join Date: Mar 2006 Posts: 4,778	and more... These data raise concerns about increased radioresistance in tumors that overexpress HER-1 and HER-2. Irradiation may activate the EGFR signaling pathway as part of a cellular protective response, and inhibitors may abrogate this response. For example, overexpression of HER-2 in MCF-7 breast cancer cell lines enhanced the activation of the transcription factor, NF-B, induced in response to radiation (9). Trastuzumab both inhibited NF-B and increased the cells' radiosensitivity. In a group of six breast cancer cell lines, high levels of HER-2 expression correlated with radioresistance (11). Treatment with trastuzumab enhanced radiosensitization, depending on the level of HER-2 expression, by reducing phosphorylation of downstream molecules Akt and MAPK. A study in breast cancer cell lines that endogenously overexpress HER-1 or HER-2 or which were transfected with HER-2 were treated with an EGFR/HER-2 inhibitor prior to irradiation (8). The drug inhibited EGFR tyrosine phosphorylation in all cell lines and increased radiosensitivity in some. A study using a novel small molecule EGFR inhibitor, CI-1033, in irradiated human breast cancer cell lines demonstrated a 23-fold increase in growth inhibition compared to radiation alone (23). Similar results have been seen in cells overexpressing HER-2 and treated with monoclonal antibody (13), an anti-erbB-2 single-chain antibody (10), and in various cell models using EGFR inhibitors, such as ZD1839 (Iressa) (11). Clinical studies of EGFR manipulation in breast cancer are limited, although there are several trials using EGFR inhibitors in the treatment of head and neck, and lung cancers (24–27).