O'dwyer Peter J, Benson Al B
University of Pennsylvania Cancer Center, Philadelphia, PA 19104, USA.
Semin Oncol. 2002 Oct;29(5 Suppl 14):10-7. doi: 10.1053/sonc.2002.35643.
Advanced colorectal carcinoma is a major cause of morbidity and mortality in the United States and other developed countries. Thus, new therapeutic strategies are urgently needed. The expression of various growth factors, growth inhibitors, and their receptors contributes to the development of colorectal cancer as well as to the proliferation and survival of malignant cells. Approximately 65% to 70% of human colon carcinomas have been shown to express the epidermal growth factor receptor (EGFR). Several investigators have reported that EGFR expression correlates with more aggressive disease and a poorer prognosis. Epidermal growth factor receptor plays a crucial role in initiating signal transduction; thus, strategies directed towards interruption of this signaling pathway have been shown to impair tumor cell proliferation. These include anti-EGFR monoclonal antibodies, immunotoxin conjugates, and EGFR tyrosine kinase inhibitors. Preclinical and clinical trials using these new therapeutic modalities appear promising in the treatment of colorectal cancer and are reviewed in this article.
晚期结直肠癌是美国及其他发达国家发病和死亡的主要原因。因此,迫切需要新的治疗策略。多种生长因子、生长抑制剂及其受体的表达促进了结直肠癌的发展以及恶性细胞的增殖和存活。约65%至70%的人类结肠癌已被证明表达表皮生长因子受体(EGFR)。几位研究人员报告称,EGFR表达与更具侵袭性的疾病和更差的预后相关。表皮生长因子受体在启动信号转导中起关键作用;因此,针对中断该信号通路的策略已被证明会损害肿瘤细胞增殖。这些策略包括抗EGFR单克隆抗体、免疫毒素偶联物和EGFR酪氨酸激酶抑制剂。使用这些新治疗方式的临床前和临床试验在结直肠癌治疗中似乎前景良好,本文将对此进行综述。