Maiese Kenneth, Chong Zhao Zhong, Shang Yan Chen, Hou Jinling
Division of Cellular and Molecular Cerebral Ischemia, Department of Neurology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
Cell Cycle. 2008 Dec 15;7(24):3829-39. doi: 10.4161/cc.7.24.7231. Epub 2008 Dec 21.
Given that cancer and related disorders affect a wide spectrum of the world's population, and in most cases are progressive in nature, it is essential that future care must overcome the present limitations of existing therapies in the absence of toxic side effects. Mammalian forkhead transcription factors of the O class (FoxOs) may fill this niche since these proteins are increasingly considered to represent unique cellular targets directed against human cancer in light of their pro-apoptotic effects and ability to lead to cell cycle arrest. Yet, FoxOs also can significantly affect normal cell survival and longevity, requiring new treatments for neoplastic growth to modulate novel pathways that integrate cell proliferation, metabolism, inflammation and survival. In this respect, members of the FoxO family are extremely compelling to consider since these transcription factors have emerged as versatile proteins that can control angiogenesis, stem cell proliferation, cell adhesion and autoimmune disease. Further elucidation of FoxO protein function during neoplastic growth should continue to lay the foundation for the successful translation of these transcription factors into novel and robust clinical therapies for cancer.
鉴于癌症及相关疾病影响着全球广泛的人群，且在大多数情况下具有进行性，未来的治疗必须在无毒性副作用的情况下克服现有疗法的当前局限性，这一点至关重要。O类哺乳动物叉头转录因子（FoxOs）可能填补这一空白，因为鉴于其促凋亡作用和导致细胞周期停滞的能力，这些蛋白质越来越被认为是针对人类癌症的独特细胞靶点。然而，FoxOs也会显著影响正常细胞的存活和寿命，因此需要针对肿瘤生长开发新的治疗方法，以调节整合细胞增殖、代谢、炎症和存活的新途径。在这方面，考虑FoxO家族成员极具吸引力，因为这些转录因子已成为多功能蛋白质，可控制血管生成、干细胞增殖、细胞黏附及自身免疫性疾病。进一步阐明FoxO蛋白在肿瘤生长过程中的功能，应会继续为将这些转录因子成功转化为新型且有效的癌症临床疗法奠定基础。
