Rega Institute for Medical Research, KULeuven, Leuven, Belgium.
Med Res Rev. 2009 Nov;29(6):903-53. doi: 10.1002/med.20159.
Thymidine phosphorylase (TP), also known as "platelet-derived endothelial cell growth factor" (PD-ECGF), is an enzyme, which is upregulated in a wide variety of solid tumors including breast and colorectal cancers. TP promotes tumor growth and metastasis by preventing apoptosis and inducing angiogenesis. Elevated levels of TP are associated with tumor aggressiveness and poor prognosis. Therefore, TP inhibitors are synthesized in an attempt to prevent tumor angiogenesis and metastasis. TP is also indispensable for the activation of the extensively used 5-fluorouracil prodrug capecitabine, which is clinically used for the treatment of colon and breast cancer. Clinical trials that combine capecitabine with TP-inducing therapies (such as taxanes or radiotherapy) suggest that increasing TP expression is an adequate strategy to enhance the antitumoral efficacy of capecitabine. Thus, TP plays a dual role in cancer development and therapy: on the one hand, TP inhibitors can abrogate the tumorigenic and metastatic properties of TP; on the other, TP activity is necessary for the activation of several chemotherapeutic drugs. This duality illustrates the complexity of the role of TP in tumor progression and in the clinical response to fluoropyrimidine-based chemotherapy.
胸苷磷酸化酶（TP），也被称为“血小板衍生的内皮细胞生长因子”（PD-ECGF），是一种酶，在包括乳腺癌和结直肠癌在内的多种实体瘤中上调。TP 通过防止细胞凋亡和诱导血管生成来促进肿瘤生长和转移。TP 水平升高与肿瘤侵袭性和预后不良相关。因此，合成了 TP 抑制剂以试图预防肿瘤血管生成和转移。TP 对于广泛使用的氟尿嘧啶前药卡培他滨的激活也是必不可少的，卡培他滨临床上用于治疗结肠癌和乳腺癌。将卡培他滨与诱导 TP 的治疗方法（如紫杉醇或放疗）联合使用的临床试验表明，增加 TP 表达是增强卡培他滨抗肿瘤疗效的一种充分策略。因此，TP 在癌症发展和治疗中具有双重作用：一方面，TP 抑制剂可以消除 TP 的致瘤和转移特性；另一方面，TP 活性对于几种化疗药物的激活是必要的。这种双重性说明了 TP 在肿瘤进展和氟嘧啶类化疗的临床反应中的作用的复杂性。
