Toi Masakazu, Atiqur Rahman Mohammad, Bando Hiroko, Chow Louis W C
Department of Clinical Trials and Research, Tokyo Metropolitan Cancer and Infectious Disease Centre, Komagome Hospital, Tokyo, Japan.
Lancet Oncol. 2005 Mar;6(3):158-66. doi: 10.1016/S1470-2045(05)01766-3.
Thymidine phosphorylase (TP) is often induced in the tumour microenvironment by physiological and chemical stress. Its induction protects cells from apoptosis and helps cell survival by stimulating nucleoside metabolism and angiogenesis. Chemotherapy often upregulates TP, which acts in cell rescue; this result indicates that TP is a crucial therapeutic target. Clinical trials for metastatic diseases have shown that TP-targeting chemotherapy with fluorouracil derivatives greatly improves the effectiveness of conventional chemotherapy for not only response but also prognosis. This new idea, the improvement of TP-inducible therapy with TP-targeting therapy, should be further investigated for early disease states, and inhibitors of TP warrant extensive investigation.
胸苷磷酸化酶(TP)在肿瘤微环境中常因生理和化学应激而被诱导。其诱导可保护细胞免于凋亡,并通过刺激核苷代谢和血管生成来帮助细胞存活。化疗常常上调TP,其发挥细胞挽救作用;这一结果表明TP是一个关键的治疗靶点。针对转移性疾病的临床试验表明,用氟尿嘧啶衍生物进行靶向TP的化疗不仅能显著提高传统化疗的疗效,还能改善预后。对于早期疾病状态,这种将靶向TP治疗与TP诱导治疗相结合的新思路应进一步研究,并且TP抑制剂值得深入研究。