Felsher Dean W
Division of Oncology, Department of Medicine, Stanford University, Stanford, CA 94305, USA.
Lymphat Res Biol. 2008;6(3-4):149-54. doi: 10.1089/lrb.2008.63403.
Cancer is largely caused by genetic events that result in the mutation of oncogenes or tumor suppressor genes, leading to cell autonomous proliferation and growth. The repair of these mutant gene products may be expected to subvert this neoplastic behavior. Indeed, oncogene inactivation can result in the elimination of all or almost all tumor cells by various mechanisms through the phenomena described as oncogene addiction. Recently, we have shown that oncogene addiction occurs through at least two broad classes of mechanisms: tumor cell intrinsic mechanisms of cellular senescence and apoptosis; and tumor cell extrinsic host-dependent mechanisms that include the shut-down of angiogenesis. We have argued that the abatement of oncogenic activity within a cancer cell not only leads to the demise of a tumor from within but also through the instruction of the restoration of the microenvironment.
癌症主要由导致癌基因或肿瘤抑制基因突变的遗传事件引起，从而导致细胞自主增殖和生长。这些突变基因产物的修复有望颠覆这种肿瘤行为。事实上，通过被称为癌基因成瘾的现象，癌基因失活可通过各种机制导致所有或几乎所有肿瘤细胞的消除。最近，我们已经表明，癌基因成瘾至少通过两大类机制发生：细胞衰老和凋亡的肿瘤细胞内在机制；以及包括血管生成关闭在内的肿瘤细胞外在宿主依赖性机制。我们认为，癌细胞内致癌活性的减弱不仅会导致肿瘤从内部消亡，还会通过指导微环境的恢复来实现。
