【诊断和治疗的分子靶点——病理学家面临的新挑战】。

S Merkelbach-Bruse, E Wardelmann, L Heukamp, N Friedrichs, R Büttner
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引用次数: 0

摘要

近十年来,分子遗传学和细胞生物学研究取得了重大进展,发现了许多调节细胞生长、分化和存活的信号转导途径。现在已经很好地理解了多种遗传畸变的积累如何导致这些信号转导途径的失调,并导致恶性转化和肿瘤进展。因此,在许多情况下,特定的肿瘤表型可能与特定的遗传变化有关。因此,分子诊断已成为肿瘤诊断的重要工具,有助于区分特定实体。此外,确定导致重要生长和生存信号激活的关键突变可以确定特定肿瘤治疗的靶标。胃肠道间质瘤(gist)提供了一个很好的例子,说明受体酪氨酸激酶的激活突变如何被用作预测肿瘤生物学和受体抑制剂治疗反应的工具。在治疗期间,继发性受体突变可能引起对治疗的抵抗,因此可能需要额外的联合治疗。因此,预测病理学和监测对新型靶向治疗的反应为病理学家提供了新的挑战,并需要广泛的分子病理学技术。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
[Molecular targets for diagnostics and therapy--new challenges for pathologists].

During the last decade significant progress in molecular genetics and cell biology was made and numerous signal transduction pathways regulating cell growth, differentiation and survival were identified. It is now fairly well understood how accumulation of multiple genetic aberrations lead to deregulation of these signal transduction pathways and cause malignant transformation and tumour progression. Therefore, in many cases specific tumour phenotypes can be linked to specific genetic changes. As a result molecular diagnostics has become an important tool for tumour diagnositics that helps to discriminate specific entities. Further, determination of critical mutations leading to activation of important growth and survival signals can identify targets for specific tumour therapies. Gastrointestinal stromal tumours (GISTs) provide an excellent example of how activating mutations in receptor tyrosine kinases can be used as a tool to predict tumour biology and response to therapy by receptor inhibitors. During therapy secondary receptor mutations may cause resistance to therapy and thus may require additional combinatorial therapies. Therefore, predictive pathology and monitoring response to novel targeted therapies provide new challenges for pathologists and require a broad spectrum of techniques in molecular pathology.

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