Felsher Dean W
Division of Oncology, Department of Medicine, Stanford University, Palo Alto, CA, USA.
APMIS. 2008 Jul-Aug;116(7-8):629-37. doi: 10.1111/j.1600-0463.2008.01037.x.
Cancer is caused by genetic changes that activate oncogenes or inactivate tumor suppressor genes. The repair or inactivation of mutant genes may be effective in the treatment of cancer. Indeed, drugs that target oncogenes can be effective in the treatment of cancer. However, it is still unclear why the inactivation of a single cancer-associated gene would ever result in the elimination of tumor cells. In experimental transgenic mouse models the consequences of oncogene inactivation depend upon the genetic and cellular context. In some cases, oncogene inactivation results in the elimination of all or almost all tumor cells through apoptosis by the phenomenon described as oncogene addiction. In other cases, oncogene inactivation predominantly results in the terminal differentiation or cellular senescence of tumor cells. In yet others, oncogene inactivation results in the apparent loss of the neoplastic properties of tumor cells, which now appear and behave like normal cells; however, upon oncogene reactivation at least some of these cells rapidly recover their neoplastic phenotype. Thus, oncogene inactivation can result in a state of tumor dormancy. Hence, understanding when and how oncogene inactivation induces apoptosis, differentiation, and senescence within a tumor will be important when developing effective strategies for the treatment of cancer.
癌症是由激活癌基因或使肿瘤抑制基因失活的基因变化引起的。突变基因的修复或失活可能对癌症治疗有效。事实上，靶向癌基因的药物可有效治疗癌症。然而，尚不清楚为何单个癌症相关基因的失活会导致肿瘤细胞的消除。在实验性转基因小鼠模型中，癌基因失活的后果取决于基因和细胞背景。在某些情况下，癌基因失活会通过被称为癌基因成瘾的现象，导致所有或几乎所有肿瘤细胞通过凋亡而被消除。在其他情况下，癌基因失活主要导致肿瘤细胞的终末分化或细胞衰老。在另外一些情况下，癌基因失活会导致肿瘤细胞的肿瘤特性明显丧失，这些细胞现在看起来和行为都像正常细胞；然而，在癌基因重新激活后，至少其中一些细胞会迅速恢复其肿瘤表型。因此，癌基因失活可导致肿瘤休眠状态。因此，在制定有效的癌症治疗策略时，了解癌基因失活何时以及如何在肿瘤内诱导凋亡、分化和衰老将非常重要。
