Hersey Peter, Zhuang L, Zhang X D
Oncology and Immunology Unit, Newcastle Mater Misericordiae Hospital, Newcastle, New South Wales, Australia.
Int Rev Cytol. 2006;251:131-58. doi: 10.1016/S0074-7696(06)51004-6.
Most anticancer agents mediate their effects through common pathways which induce apoptosis or in some cases necrosis of cancer cells. The apoptotic pathways are regulated by Bcl-2 family proteins, which include both pro- and anti-apoptotic members. Much is known about the interactions of these proteins involved in apoptosis and this information is being utilized in the development of new reagents that may be used to treat patients with cancers. The inhibitor of apoptosis family of proteins constitute a second group of proteins which inhibit the effector caspases. Reagents that inhibit their activity are also under development. Resistance of cancer cells to treatment can in many instances be attributed to activation of intracellular signal pathways involved in survival, such as the Ras-Raf-MEK-ERK1/2 or the P13K-Akt pathway. Again, much has been learned about the control of these pathways and their activation of resistance mechanisms. Inhibitors of such pathways are being evaluated in preclinical and clinical studies and are showing promise as a new class of anticancer agents. Much of the progress in future studies will likely depend on the ability to target these new treatments to particular subgroups of patients with tumor characteristics that make them responsive to the agents in question.
大多数抗癌药物通过诱导癌细胞凋亡或在某些情况下坏死的共同途径发挥作用。凋亡途径由Bcl-2家族蛋白调节，该家族蛋白包括促凋亡和抗凋亡成员。关于这些参与凋亡的蛋白之间的相互作用已有很多了解，这些信息正被用于开发可用于治疗癌症患者的新试剂。凋亡抑制蛋白家族构成了另一组抑制效应半胱天冬酶的蛋白。抑制其活性的试剂也在研发中。癌细胞对治疗的耐药性在许多情况下可归因于参与细胞存活的细胞内信号通路的激活，如Ras-Raf-MEK-ERK1/2或P13K-Akt通路。同样，关于这些通路的控制及其耐药机制的激活也有很多了解。此类通路的抑制剂正在临床前和临床研究中进行评估，并显示出作为一类新型抗癌药物的前景。未来研究的许多进展可能取决于能否将这些新疗法靶向具有特定肿瘤特征的患者亚组，这些特征使他们对相关药物有反应。
