Gefitinib-trastuzumab combination on hormone-refractory prostate cancer xenograft

Area of Science:

• Oncology
• Molecular Biology

Background:

• Hormone-refractory prostate cancer (HRPC) remains a challenge with limited treatment options.
• Epidermal growth factor receptor (EGFR) and HER-2 are potential therapeutic targets in HRPC.

Purpose of the Study:

• To investigate the combined effects of gefitinib and trastuzumab on the androgen-refractory prostate cancer cell line DU145.
• To evaluate the impact of these drug combinations with radiotherapy (RT) on tumor growth, proliferation, and apoptosis.

Main Methods:

• DU145 cell line (expressing EGFR and HER-2) was treated with gefitinib and trastuzumab, alone and in combination.
• In vivo studies were conducted using mice to assess tumor volume reduction.
• Analysis of factors related to cell proliferation (p27) and apoptosis (Bax:Bcl2 ratio) was performed.

Main Results:

• Gefitinib demonstrated more pronounced anti-tumor effects than trastuzumab.
• The gefitinib-trastuzumab combination in mice resulted in tumor volume reduction inferior to predicted additive effects.
• Trastuzumab attenuated gefitinib-induced increases in p27 expression and the Bax:Bcl2 ratio.
• Gefitinib-RT showed additive anti-tumor effects, while trastuzumab-RT showed less than additive effects.

Conclusions:

• The combination of gefitinib and trastuzumab may not be additive in HRPC, with potential interference from trastuzumab.
• Radiotherapy combinations require careful consideration, as gefitinib-RT appears additive while trastuzumab-RT does not.
• These findings have implications for designing future clinical trials involving HER inhibitors in HRPC.