Lung Cancer Research Today is a free monthly online journal that collates and summarizes the latest research about Lung Cancer, including details on symptoms, smoking, genetics, treatment, causes.

Therapeutic targeting of the endothelin a receptor in human nasopharyngeal carcinoma.

Mai HQ, Zeng ZY, Feng KT, Ye YL, Zhang CQ, Liang WJ, Guo X, Mo HY, Hong MH

State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China.

The endothelin A receptor (ET(A)R) autocrine pathway is overexpressed in many malignancies, including nasopharyngeal carcinoma (NPC). In this tumor, ET(A)R expression is an independent determinant of survival and a robust independent predictor of distant metastasis. To evaluate whether ET(A)R represents a new target in NPC treatment, we tested the therapeutic role of ET(A)R in NPC. Cell proliferation was inhibited by the ET(A)R-selective antagonist ABT-627 in two ET(A)R-positive NPC cells in a dose-dependent manner. Proliferation of ET(A)R-negative NPC cells was not decreased. ET(A)R blockade also resulted in sensitization to cisplatin and 5-fluorouracil-induced apoptosis. In nude mice, ABT-627 inhibited the growth of NPC cell xenografts. Combined treatment of ABT-627 with the cytotoxic drug cisplatin or 5-fluorouracil produced additive antitumor effects. The antitumor activity of ABT-627 was demonstrated finally on an experimental lung metastasis by a reduction in the number of tumors. These results support the rationale of combining ABT-627 with current standard chemotherapy to further improve the therapeutic ratio in the treatment of NPC.

Published 2 November 2006 in Cancer Sci, 97(12): 1388-95.
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