Department R4CD, Global Pharmaceutical R&D, Abbott Laboratories, Building AP-10, 100 Abbott Park Road, Abbott Park, IL 60064, USA.
Mol Diagn Ther. 2012 Dec;16(6):347-56. doi: 10.1007/s40291-012-0003-6.
Cancer cells persist by resisting programmed cell death or apoptosis. In particular, an imbalance of proteins that regulate apoptosis leads to lack of response to apoptotic stimuli. Thus, restoring the ability of cancer cells to undergo apoptosis is highly desirable. One apoptosis pathway, the intrinsic pathway, involves perturbation of the mitochondria. The major players of this pathway are the members of the B cell CLL/lymphoma 2 (BCL2) family. Currently, three BCL2 antagonists are in clinical trials for cancer treatment. While these antagonists show various specificity and potency, the development of companion diagnostics is crucial for developing these compounds into viable cancer treatments. In this review we describe predictive and pharmacodynamic biomarkers for these agents. Future directions on biomarker development for this class of antagonist are also discussed.
癌细胞通过抵抗程序性细胞死亡或细胞凋亡而存活。特别是，调节细胞凋亡的蛋白质失衡会导致对凋亡刺激无反应。因此，恢复癌细胞发生凋亡的能力是非常可取的。一种凋亡途径，即内在途径，涉及线粒体的扰动。该途径的主要参与者是 B 细胞 CLL/淋巴瘤 2 (BCL2) 家族的成员。目前，有三种 BCL2 拮抗剂正在进行癌症治疗的临床试验。虽然这些拮抗剂显示出不同的特异性和效力，但开发伴随诊断对于将这些化合物开发成可行的癌症治疗方法至关重要。在这篇综述中，我们描述了这些药物的预测性和药效动力学生物标志物。还讨论了针对这类拮抗剂的生物标志物开发的未来方向。
