进展期胃癌的分子靶向治疗

过去的二十年里,进展期胃癌患者通过治疗后可以改善生活质量及延长生存期,但是其治疗方法并没有获得显著进展。虽然胃癌的中位生存期大约在7~11个月,且存活超过2年的已经〉10%,但是,对于进展期胃癌患者来说,其最合适的一线化疗方案一直存在争议,且大多数人对化疗仍持有偏见。最近,肿瘤生物学的显著进展促进了靶向致癌关键途径的新药物研究。在国际随机研究中,对进展期胃癌来说,多数分子靶向因子被证实有效,一种抗HER-2单克隆抗体（曲妥珠单抗）显示在抗HER-2阳性的进展期胃癌方面有抗肿瘤活性。然而,只有20%的HER-2阳性的进展期胃癌患者在此获益。因此,发展更有效的因子和鉴别预测及预后的标记物因子来选择哪些患者能从特定的化疗方案和靶向治疗中获益显得至关重要。本文就进展期胃癌的靶向治疗作一综述。

Molecular targeted therapy for advanced gastric cancer

Although medical treatment has been shown to improve quality of life and prolong survival, no significant progress has been made in the treatment of advanced gastric cancer （AGC） within the last two decades. Thus the optimum standard first-line chemotherapy regimen for AGC remains debatable： and most responses to chemotherapy are partial and of short duration; the median survival is approximately 7 to 11 months, and survival rate at 2 years is exceptionally〉10%. Recently, remarkable progress in tumor biology has led to the development of new agents that target critical aspects of oncogenic pathways. For AGC, many molecular targeting agents have been evaluated in international randomized studies, and trastuzumab （an anti-HER-2 monoclonal antibody） has shown antitumor activity against HER-2-positive AGC. However, this benefit is limited to only 20% patients with AGC （patients with HER-2-positive AGC）. Therefore, there remains a critical need for both the development of more effective agents and the identification of molecular predictive and prognostic markers to select those patients who will benefit most from specific chemotherapeutic regimens and targeted therapies. This article reviewed the targeted therapy for advanced gastric cancer.