Effects of Imatinib mesylate on the radio- and chemosensitivity of breast carcinoma cell lines

Breast cancer treatment is based on a combination of adjuvant chemotherapy followed by radiotherapy. With the tyrosine kinase inhibitors new targeted drugs are available like Imatinib mesylate, a selective inhibitor of bcr-abl, PRGFR α, β and c-kit. The purpose of this study was to determine whether Imatinib has an influence on the effectiveness of radiotherapy in breast cancer cell lines and if a combination of Imatinib with standard chemotherapy could lead to increased cytoreduction.

Colony-forming tests of MCF 7 and MDA MB 231 were used to study differences in cell proliferation under incubation with Imatinib and radiation(2Gy/d x5). Changes in expression and phosphorylation of target receptors were detected by western blot. Cell proliferation assays were performed combining Imatinib with Vinorelbine, Paclitaxel and Doxorubicine.

The combination of Imatinib and radiotherapy showed a significantly stronger inhibition of cell proliferation compared to single radiotherapy. Differences in PDGFR expression could not be detected but receptor phosphorylation was significantly inhibited when treated with Imatinib. Combination of Imatinib with standard chemotherapy leads to a further increase of cell growth inhibition compared to single treatment.

Imatinib combined with radiotherapy leads in both cell lines to a significant benefit which might be influenced through inhibition of PDGFR phosphorylation. Combining Imatinib with chemotherapy enhances cytoreductive effects. Therefore lower doses with fewer side effects might be used. Further in vivo studies are needed to evaluate the benefit of Imatinib in combination with radiotherapy and chemotherapy in the treatment of breast cancer.

tyrosine kinase inhibitor - targeted therapy - radiosensitivity - PDGFR