ZD1839的大肠癌进展

文题：Development of ZD1839 in colorectal cancer
作者：Edwin C. Douglass
杂志全名：seminars in oncology
年份，卷（期）：起始页码：2003，30（3）S6：17-22
英文摘要：Colorectal cancer is one of the most frequent human malignancies. Therapeutic options are mainly limited to chemotherapy with 5-fluorouracil in various schedules or in combination with irinotecan and oxaliplatin; however, novel approaches are also in development. These new agents specifically attack molecular targets involved in tumor biology. One such target is the epidermal growth factor receptor (EGFR), which is highly expressed in many tumors and is associated with a poor prognosis. The EGFR plays a key role in cell proliferation and has been implicated in several processes that mediate cancer progression. ZD1839 is an orally active, selective EGFR tyrosine kinase inhibitor that has shown extensive preclinical activity and favorable tolerability in advanced clinical trials in a variety of tumors. In colorectal cancer cells, ZD1839 has shown both in vitro and in vivo antitumor activity as monotherapy or in combination with cytotoxic agents such as paclitaxel and irinotecan. Preclinical data have also shown that ZD1839 reverses resistance to irinotecan and enhances its efficacy by improving oral bioavailability. These studies indicate that EGFR inhibition by ZD1839 may have a valuable role in the treatment of colorectal cancer, and clinical studies in patients with colorectal cancer are ongoing.
中文摘要：大肠癌是人类最常见的恶性肿瘤之一。治疗的选择主要是以各种不同时间应用5-氟尿嘧啶或联合依立替康和奥沙力铂，然而各种新的治疗方法也有所进展。这些新药特异性攻击涉及肿瘤生物学的分子靶向。表皮生长因子受体就是一个这样的靶向，它在许多肿瘤中都有高度表达，是预后不良因素。表皮生长因子受体在细胞增殖有重要作用，并与肿瘤进展相关。ZD1839是一种口服的、有效的选择性落氨酸激酶抑制剂，它在临床前期显示了广泛的抗肿瘤活性，并在许多肿瘤的进一步实验中显示了良好的耐受性。单用ZD1839或与其他细胞毒性药物如紫杉醇和依立替康联合应用无论在大肠癌细胞的体内或体外试验中，都显示了抗肿瘤活性。临床前期数据显示ZD1839能够逆转依立替康耐药，并且通过提高它的口服生物利用度可以增强活性。这些研究说明通过ZD1839对表皮生长因子受体的抑制，可能会在大肠癌的治疗中有相当的价值。目前该药的大肠癌临床试验正在进行中。