Cancer stromal targeting (CAST) therapy

被引:77
作者
Matsumura, Yasuhiro [1 ]
机构
[1] Natl Canc Ctr Hosp E, Res Ctr Innovat Oncol, Investigat Treatment Div, Kashiwa, Chiba 2778577, Japan
基金
日本学术振兴会;
关键词
Cancer stromal targeting; Blood coagulation; Fibrin; Collagen; 4; Immunoconjugate; IMMUNOCONJUGATE THERAPY; TUMOR MICROENVIRONMENT; VASCULAR-PERMEABILITY; DRUG; THERAPEUTICS; ANTIBODY; ACCUMULATION; CHEMOTHERAPY; FIBROBLASTS; MECHANISM;
D O I
10.1016/j.addr.2011.12.010
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Despite great advances in cell and molecular biology, pharmacology and medicine, there is to date no antitumor drug available which can specifically kill tumor cells in the human body without damaging normal tissue, because it has not been possible to find a truly cancer specific molecule to target. Low molecular weight (MW) anticancer drugs extravasate easily from normal vessels in the body causing drug adverse effects. Conversely, high MW anti-tumor agents including antibodies against cancer cell antigens, accumulate selectively in tumors because of their leaky vasculature. However, most human solid tumors possess abundant intercellular connective tissue, hindering diffusion of such macromolecules. That is why immunoconjugate therapy for stroma rich common solid cancer has not yet proved successful in clinics. In this review, I describe a successful new strategy that overcomes the above contradictory drawbacks by conjugating a small MW cyototoxic drug with an antibody against particular components of tumor stroma. Stroma-targeting immunconjugates bound to the stroma to create a scaffold, from which sustained release of cytotoxic agent occurred and subsequently diffused throughout the tumor tissue to damage both tumor cells and tumor vessels. Cancer-stroma targeting (CAST) therapy was thus validated as a new modality of oncological therapy, especially for refractory, stromal-rich cancers. (C) 2011 Elsevier B.V. All rights reserved.
引用
收藏
页码:710 / 719
页数:10
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