MLL Munich Leukemia Laboratory, Munich, Germany.
Handb Exp Pharmacol. 2023;280:35-64. doi: 10.1007/164_2022_608.
The development and approval of the tyrosine kinase inhibitor imatinib in 2001 has heralded the advance of directed therapy options. Today, an armamentarium of targeted therapeutics is available and enables the use of precision medicine in non-solid cancer. Precision medicine is guided by the detection of tumor-specific and targetable characteristics. These include pathogenic fusions and/or mutations, dependency on specific signaling pathways, and the expression of certain cell surface markers. Within the first part, we review approved targeted therapies for the compound classes of small molecule inhibitors, antibody-based therapies and cellular therapies. Particular consideration is given to the underlying pathobiology and the respective mechanism of action. The second part emphasizes on how biomarkers, whether they are of diagnostic, prognostic, or predictive relevance, are indispensable tools to guide therapy choice and management in precision medicine. Finally, the examples of acute myeloid leukemia, chronic lymphocytic leukemia, and chronic myeloid leukemia illustrate how integration of these biomarkers helps to tailor therapy.
2001 年酪氨酸激酶抑制剂伊马替尼的开发和批准标志着靶向治疗选择的进步。如今，一系列靶向治疗药物已经问世，使得精准医学在非实体瘤癌症中得以应用。精准医学以检测肿瘤特异性和可靶向特征为指导。这些特征包括致病融合和/或突变、对特定信号通路的依赖性以及某些细胞表面标志物的表达。在第一部分中，我们回顾了已批准的用于小分子抑制剂、基于抗体的疗法和细胞疗法的化合物类别的靶向治疗药物。特别考虑了潜在的病理生物学和各自的作用机制。第二部分强调了生物标志物（无论是诊断、预后还是预测相关）如何成为指导精准医学中治疗选择和管理的不可或缺的工具。最后，急性髓系白血病、慢性淋巴细胞白血病和慢性髓性白血病的例子说明了这些生物标志物的综合应用如何有助于定制治疗。
