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Abstract：
Many cancer diseases, e.g., prostate cancer and lung cancer, develop very slowly. Common chemotherapeutics like vincristine, vinblastine and taxol target cancer cells in their proliferating states. In slowly developing cancer diseases only a minor part of the malignant cells will be in a proliferative state, and consequently these drugs will exert a concomitant damage on rapidly proliferating benign tissue as well. A number of toxins possess an ability to kill cells in all states independently of whether they are benign or malignant. Such toxins can only be used as chemotherapeutics if they can be targeted selectively against the tumors. Examples of such toxins are mertansine, calicheamicins and thapsigargins, which all kill cells at low micromolar or nanomolar concentrations. Advanced prodrug concepts enabling targeting of these toxins to cancer tissue comprise antibody-directed enzyme prodrug therapy (ADEPT), gene-directed enzyme prodrug therapy (GDEPT), lectin-directed enzyme-activated prodrug therapy (LEAPT), and antibody-drug conjugated therapy (ADC), which will be discussed in the present review. The review also includes recent examples of protease-targeting chimera (PROTAC) for knockdown of receptors essential for development of tumors. In addition, targeting of toxins relying on tumor-overexpressed enzymes with unique substrate specificity will be mentioned.
摘要：
许多癌症疾病，例如，前列腺癌和肺癌,发展非常缓慢。常见的化疗药物如长春新碱,长春碱和紫杉醇靶向处于其增殖状态的癌细胞。在缓慢发展的癌症疾病中，只有一小部分恶性细胞处于增殖状态，因此，这些药物也会对快速增殖的良性组织产生伴随的损害。许多毒素具有杀死处于所有状态的细胞的能力,而不管它们是良性的还是恶性的。如果这些毒素可以选择性地靶向肿瘤,则它们只能用作化学治疗剂。这类毒素的例子是mertansine，Calicheamicins和thapsigargins,它们都在低微摩尔或纳摩尔浓度下杀死细胞。能够将这些毒素靶向癌组织的高级前药概念包括抗体导向的酶前药治疗（ADEPT），基因导向酶前药治疗（GDEPT），凝集素定向酶激活前药治疗（LEAPT），和抗体-药物偶联疗法（ADC），这将在本审查中讨论。该综述还包括蛋白酶靶向嵌合体（PROTAC）的最新实例，用于敲低肿瘤发展所必需的受体。此外,将提到依赖于具有独特底物特异性的肿瘤过表达的酶的毒素靶向。
