Dual inhibition of the epidermal growth factor and vascular endothelial growth factor phosphorylation for antivascular therapy of human prostate cancer in the prostate of nude mice.

Androgen-independent prostate cancer (PCa) may be susceptible to modulation of the tumor microenvironment. We determined whether a dual tyrosine kinase inhibitor (AEE788) of the epidermal growth factor receptor (EGF-R) and vascular endothelial growth factor receptor (VEGF-R) combined with chemotherapy can produce therapy of human PCa in nude mice. PC-3MM2 human PCa cells were injected into the prostate of nude mice. Three days later, the mice were randomized into four groups: saline control, paclitaxel, AEE788, and AEE788 and paclitaxel. The mice were treated for 5 weeks and necropsied. Tumor incidence, weight, and incidence of lymph node metastasis were recorded. Tumor tissue was analyzed immunohistochemically. Treatment of mice with AEE788 or AEE788 plus paclitaxel significantly decreased tumor incidence, total tumor weight, and incidence of lymph node metastasis. AEE788 treatment alone or in combination with paclitaxel inhibited the phosphorylation of EGF-R and VEGF-R on tumor cells and tumor-associated endothelial cells. Therapeutic efficacy correlated with an increase in apoptosis of tumor cells and tumor-associated endothelial cells. Blockade of EGF-R and VEGF-R signaling pathways coupled with chemotherapy suppressed the progressive growth and metastasis of human PCa cells growing orthotopically in nude mice.

Yazici S ，Kim SJ ，Busby JE ，He J ，Thaker P ，Yokoi K ，Fan D ，Fidler IJ ... -  《PROSTATE》

Blockade of epidermal growth factor receptor signaling in tumor cells and tumor-associated endothelial cells for therapy of androgen-independent human prostate cancer growing in the bone of nude mice.

Kim SJ ，Uehara H ，Karashima T ，Shepherd DL ，Killion JJ ，Fidler IJ ... -  《CLINICAL CANCER RESEARCH》

Simultaneous blockade of platelet-derived growth factor-receptor and epidermal growth factor-receptor signaling and systemic administration of paclitaxel as therapy for human prostate cancer metastasis in bone of nude mice.

Kim SJ ，Uehara H ，Yazici S ，Langley RR ，He J ，Tsan R ，Fan D ，Killion JJ ，Fidler IJ ... -  《CANCER RESEARCH》

Antivascular therapy for orthotopic human ovarian carcinoma through blockade of the vascular endothelial growth factor and epidermal growth factor receptors.

Thaker PH ，Yazici S ，Nilsson MB ，Yokoi K ，Tsan RZ ，He J ，Kim SJ ，Fidler IJ ，Sood AK ... -  《CLINICAL CANCER RESEARCH》

Dual epidermal growth factor receptor and vascular endothelial growth factor receptor inhibition with NVP-AEE788 for the treatment of aggressive follicular thyroid cancer.

Younes MN ，Yazici YD ，Kim S ，Jasser SA ，El-Naggar AK ，Myers JN ... -  《CLINICAL CANCER RESEARCH》