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[分子靶向抗癌治疗——简要评估]

[Molecularly-targeted anticancer treatments - a short appraisal].

作者信息

Joerger Markus

机构信息

Medizinische Onkologie und Hämatologie, Kantonsspital, St. Gallen.

出版信息

Ther Umsch. 2019 Sep;76(4):179-185. doi: 10.1024/0040-5930/a001082.

DOI:10.1024/0040-5930/a001082
PMID:31498038
Abstract

Molecularly-targeted anticancer treatments - a short appraisal Molecularly-targeted or personalized systemic treatment has substantially transformed modern oncology, and has improved the prognosis of many tumor entities, in particular advanced solid and hematological malignancies. The bulk of molecularly-targeted anticancer drugs comprise small orally administered molecules, most prominently the tyrosine kinase inhibitors (TKI). The respective tumor entities treated by those drugs typically harbour specific genetic aberrations that we often call 'driver mutations', referring to their transforming and tumorigenic properties. Molecularly-targeted anticancer drugs fit to these genetic aberrations as they are able to specifically inhibit growth-stimulating signals. The success story of modern TKI's started 1999 with the use of the anti-BCR / ABL TKI imatinib in chronic myelogenous leucemia (CML) that enables those patients to achieve a virtually normal life expectancy. Since then, many molecularly-targeted anticancer drugs and TKI's have been approved for a wide range of malignancies. The next level of personalized oncological treatment will have to deal with much less frequent genetic aberrations that are inherently more difficult to spot in the tumor and to study. Newer techniques including next-generation sequencing (NGS) will help cancer specialists to screen their patients for genetic aberrations and get the most benefit from personalized oncology.

摘要

分子靶向抗癌治疗——简要评估 分子靶向或个性化全身治疗已极大地改变了现代肿瘤学,并改善了许多肿瘤实体的预后,尤其是晚期实体瘤和血液系统恶性肿瘤。大部分分子靶向抗癌药物包括口服小分子,最突出的是酪氨酸激酶抑制剂(TKI)。这些药物所治疗的相应肿瘤实体通常存在特定的基因畸变,我们常将其称为“驱动突变”,这是指它们的转化和致瘤特性。分子靶向抗癌药物能够特异性抑制生长刺激信号,因而与这些基因畸变相匹配。现代TKI的成功故事始于1999年,当时抗BCR/ABL TKI伊马替尼用于治疗慢性粒细胞白血病(CML),使这些患者能够获得几乎正常的预期寿命。从那时起,许多分子靶向抗癌药物和TKI已被批准用于多种恶性肿瘤。个性化肿瘤治疗的下一个阶段将不得不应对更罕见的基因畸变,而这些畸变在肿瘤中本身就更难发现和研究。包括下一代测序(NGS)在内的新技术将帮助癌症专家筛查患者的基因畸变,并从个性化肿瘤学中获得最大益处。

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