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Targeted Therapy: Its Status and Promise in Selected Solid Tumors Part I: Areas of Major Impact

机译：靶向治疗：其在部分实体瘤中的地位和承诺第一部分：主要影响领域

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摘要

"Targeted therapy" is becoming the centerpiece of current therapeutic strategies, and is often mentioned as the desirable direction for future progress. Why and how it is replacing past approaches in the management of solid tumors is the subject of this two-part overview. Here, in Part I, we describe areas where major inroads were initially achieved by targeting angio-genesis (central to the biology of renal cell carcinoma and hepatocellular cancer) and by unraveling pathways in the heterogeneous tumors of mesenchy-ma| origin-spurred by the identification of c-Kit-activating mutations in gastrointestinal stromal tumors (GIST) and the regressions that ensued when tumors harboring these mutations were exposed to the tyrosine kinase inhibitor imatinib (Gleevec). More recently, the successes in the treatment of the notoriously refractory malignant melanoma via the targeting of a specific BRAF mutation and via immune activation represent an unprecedented achievement of this new therapeutic direction. For each cancer discussed in the first part of our overview, as well as in Part II, which will deal with more common cancers, we briefly cover the tumor biology, how targeting was achieved, the introduction of immune modulation or immune-conjugates, and the impact these therapies are having in the disease.
机译：“靶向治疗”正成为当前治疗策略的核心，并且经常被提及为未来发展的理想方向。本部分分为两部分，主题是为什么以及如何取代过去的实体瘤治疗方法。在本文的第一部分中，我们描述了最初通过靶向血管生成（在肾细胞癌和肝细胞癌的生物学研究中处于中心地位）以及通过阐明间质瘤异质性肿瘤中的途径而取得重大进展的领域。通过鉴定胃肠道间质瘤（GIST）中的c-Kit激活突变以及源自将携带这些突变的肿瘤暴露于酪氨酸激酶抑制剂伊马替尼（Gleevec）所引起的回归，来激发起源。最近，通过靶向特定的BRAF突变和通过免疫活化治疗难治性难治性恶性黑色素瘤的成功代表了这一新治疗方向的空前成就。对于我们概述的第一部分以及第二部分（将讨论更常见的癌症）中讨论的每种癌症，我们简要介绍了肿瘤生物学，如何实现靶向，引入免疫调节或免疫偶联物，以及这些疗法对疾病的影响。

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