Targeting cancer with telomerase: commentary re Q. Huang et al., a novel conditionally replicative adenovirus vector targeting telomerase-positive tumor cells. Clin. Cancer Res., 10: 1439-1445, 2004.
Targeting cancer with telomerase: commentary re Q. Huang et al., a novel conditionally replicative adenovirus vector targeting telomerase-positive tumor cells. Clin. Cancer Res., 10: 1439-1445, 2004.
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用端粒酶靶向癌症：对 Q. Huang 等人的评论，一种针对端粒酶阳性肿瘤细胞的新型条件复制腺病毒载体。
DOI：
10.1158/1078-0432.ccr-04-0060
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Hahn,WilliamC
中科院分区：
文献类型：
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作者：
Hahn,WilliamC
在过去的50年里，抗生素、疫苗和其他抗菌剂的开发和广泛使用大大降低了由感染因子引起的死亡率。这些治疗成功在很大程度上是通过鉴定和开发专门针对微生物表达的分子的方法来实现的。这种模式不仅继续推动开发新的抗菌剂和疫苗的努力，而且还刺激了将这种方法应用于癌症治疗的努力。事实上，许多实验室的共同努力已经确定了癌细胞特有的特定分子改变。然而，与微生物不同，癌细胞起源于正常前体，并且由这种恶性细胞表达的大多数蛋白质也存在于正常细胞中。此外，许多与人类肿瘤相关的分子变化是蛋白质表达水平的细微氨基酸取代或改变。正常细胞和恶性细胞的这种总体相似性使这种在感染性疾病中如此有效的范例应用于癌症治疗变得复杂。此外，由于一些癌症相关分子不是持续恶性潜能所必需的，因此选择下调或失去预期靶点表达的癌细胞代表了获得性耐药的主要机制。尽管存在这些挑战，但最近的研究表明，这种药物开发模式将在癌症中取得成功。使用小分子或抗体（如Gleevec、Herceptin和Rituximab）的方法提供了很好的例子，说明靶向癌症相关分子（甚至是一些正常细胞表达的分子）的治疗方法不仅有效，而且比传统化疗毒性更低。挑战仍然是识别和利用对肿瘤维持至关重要的其他分子。
During the past 50 years, the development and widespread use of antibiotics, vaccines, and other antimicrobial agents has dramatically reduced the mortality caused by infectious agents. These therapeutic successes were achieved, in large part, by the identification and development of approaches that target molecules expressed exclusively by microbes. This paradigm not only continues to drive efforts to develop new antimicrobials and vaccines but has also stimulated efforts to apply this approach to the treatment of cancer. Indeed, concerted efforts from many laboratories have identified specific molecular alterations unique to cancer cells. However, unlike microbes, cancer cells originate from normal precursors, and the majority of proteins expressed by such malignant cells are also found in normal cells. Moreover, many of the molecular changes associated with human tumors are subtle amino acid substitutions or alterations in the level of protein expression. This overall similarity of normal and malignant cells complicates the application of this paradigm that has worked so well in infectious disease to cancer treatment. In addition, because some cancer-associated molecules are not required for continued malignant potential, selection of cancer cells that have down-regulated or lost expression of the intended target represents a major mechanism of acquired resistance. Despite these challenges, recent work indicates that this model for drug development will succeed in cancer. Approaches using small molecules or antibodies such as Gleevec, Herceptin, and Rituximab provide excellent examples of how targeting cancer-associated molecules, even those expressed by some normal cells, can lead to therapeutics that are not only effective but also less toxic than traditional chemotherapy. The challenge remains to identify and exploit other molecules critical to tumor maintenance.