胰腺癌的分子靶向药物治疗

Molecular-targeted agents in pancreatic cancer

胰腺癌发病率在世界范围内近年来有明显增加趋势,其首选治疗方法为手术切除,但因多数不能早期发现而切除率低。吉西他滨是目前晚期胰腺癌化疗的一线方案。其他化疗药物与吉西他滨联合治疗胰腺癌未发现能显著延长患者生存期,分子靶向药物成为目前研究的焦点。尽管用基质金属蛋白酶抑制剂和法呢基转移酶抑制剂治疗晚期胰腺癌的临床研究未得到满意的结果,但将VEGF和EGFR单克隆抗体,酪氨酸激酶抑制剂,COX-2抑制剂及其他免疫治疗方法用于胰腺癌的临床研究结果都令人鼓舞。

Despite the acceptance of gemcitabine as the standard first-line agent for the treatment of advanced pancreatic cancer as well as the improved response rates seen with gemcitabine combinations,novel therapies are needed for this disease,which has one of the lowest survival rates.The growing understanding of the molecular basis of pancreatic cancer and the recent introduction of targeted therapeutic agents have initiated novel studies that have the potential to improve on existing treatments.We review the rationale and the clinical studies of therapeutic agents that target some of the molecular abnormalities commonly found in pancreatic cancer.Phase Ⅲ studies of MMPIs,alone or in combination with gemcitabine,and phase Ⅲ studies of FTIs have produced disappointing results.The result of phase Ⅱ or Ⅲ trials of monoclonal antibodies against growth factors or their receptors,tyrosine-kinase inhibitors are encouraging.Targeted agents may improve the prognosis of pancreatic cancer.