Peptide phage display: Opportunities for development of personalized anti-cancer strategies
Peptide phage display: Opportunities for development of personalized anti-cancer strategies
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DOI：
10.2174/187152006774755492
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发表时间：
2006-01-01
影响因子：
2.8
通讯作者：
Cox, N. R.
中科院分区：
文献类型：
--
作者：
Samoylova, T. I.;Morrison, N. E.;Cox, N. R.
个性化治疗对癌症患者至关重要，因为(1)癌症是一种高度异质性的疾病，在相同类型和级别的癌症患者中，肿瘤细胞表面标志物的表达和分布存在重大的分子差异；(2)随着癌症的进展，细胞突变往往会积累，进一步增加肿瘤的异质性；(3)目前使用的癌症治疗方法往往对正常细胞有毒性，造成在其他疾病中罕见的严重副作用。为了防止副作用和提高疗效，细胞毒性治疗应该是有针对性的，并且在治疗之前应该对每个患者进行癌症目标的分析。噬菌体展示技术利用噬菌体颗粒上表达的蛋白质组合文库，可以选择特异性结合到癌细胞上。这种癌症特异性分子可用于各种应用，包括细胞特异性靶向分子的鉴定；细胞表面生物标志物的鉴定；从个体癌症患者获得的标本分析，以及为个性化治疗设计基于肽的抗癌疗法。这篇综述的重点是针对细胞表面的肽噬菌体展示策略，因为许多在癌症中重要的生物标志物是位于细胞膜外的差异表达分子。
Personalized medicine is critical for cancer patients, because (1) cancer is a highly heterogeneous disease with major molecular differences in the expression and distribution of tumor cell surface markers among patients with the same type and grade of cancer, (2) cellular mutations tend to accumulate as cancer progresses, further increasing tumor heterogeneity, and (3) currently used cancer therapies often are toxic to normal cells, causing severe side effects rarely seen in other diseases. To prevent side effects and to improve effectiveness, cytotoxic therapies should be targeted and each patient should be profiled for the presence of cancer targets before the therapy is administered. Phage display technology utilizes combinatorial libraries of proteins expressed on phage particles that can be selected for specific binding to cancer cells. Such cancer-specific molecules can be used in a variety of applications, including identification of cell-specific targeting molecules; identification of cell surface biomarkers; profiling of specimens obtained from individual cancer patients, and the design of peptide-based anti-cancer therapeutics for personalized treatments. This review is focused on peptide phage display strategies that target cell surfaces because many biomarkers important in cancer are differentially expressed molecules located on the outside of the cell membranes.