Arap W, Pasqualini R, Ruoslahti E
Cancer Research Center, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
Science. 1998 Jan 16;279(5349):377-80. doi: 10.1126/science.279.5349.377.
In vivo selection of phage display libraries was used to isolate peptides that home specifically to tumor blood vessels. When coupled to the anticancer drug doxorubicin, two of these peptides-one containing an alphav integrin-binding Arg-Gly-Asp motif and the other an Asn-Gly-Arg motif-enhanced the efficacy of the drug against human breast cancer xenografts in nude mice and also reduced its toxicity. These results indicate that it may be possible to develop targeted chemotherapy strategies that are based on selective expression of receptors in tumor vasculature.
利用噬菌体展示文库在体内进行筛选,以分离能够特异性归巢至肿瘤血管的肽段。当与抗癌药物阿霉素偶联时,其中两个肽段——一个含有αv整合素结合的精氨酸-甘氨酸-天冬氨酸基序,另一个含有天冬酰胺-甘氨酸-精氨酸基序——增强了该药物对裸鼠人乳腺癌异种移植瘤的疗效,同时降低了其毒性。这些结果表明,基于肿瘤脉管系统中受体的选择性表达开发靶向化疗策略或许是可行的。