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作为抗衰老药物的选择性抗癌剂。

Selective anti-cancer agents as anti-aging drugs.

作者信息

Blagosklonny Mikhail V

机构信息

Cell Stress Biology; Roswell Park Cancer Institute; Buffalo, NY USA.

出版信息

Cancer Biol Ther. 2013 Dec;14(12):1092-7. doi: 10.4161/cbt.27350. Epub 2013 Nov 27.

Abstract

Recent groundbreaking discoveries have revealed that IGF-1, Ras, MEK, AMPK, TSC1/2, FOXO, PI3K, mTOR, S6K, and NFκB are involved in the aging process. This is remarkable because the same signaling molecules, oncoproteins and tumor suppressors, are well-known targets for cancer therapy. Furthermore, anti-cancer drugs aimed at some of these targets have been already developed. This arsenal could be potentially employed for anti-aging interventions (given that similar signaling molecules are involved in both cancer and aging). In cancer, intrinsic and acquired resistance, tumor heterogeneity, adaptation, and genetic instability of cancer cells all hinder cancer-directed therapy. But for anti-aging applications, these hurdles are irrelevant. For example, since anti-aging interventions should be aimed at normal postmitotic cells, no selection for resistance is expected. At low doses, certain agents may decelerate aging and age-related diseases. Importantly, deceleration of aging can in turn postpone cancer, which is an age-related disease.

摘要

最近的重大发现表明,胰岛素样生长因子-1(IGF-1)、Ras、丝裂原活化蛋白激酶(MEK)、腺苷酸活化蛋白激酶(AMPK)、结节性硬化复合物1/2(TSC1/2)、叉头框蛋白O(FOXO)、磷脂酰肌醇-3激酶(PI3K)、哺乳动物雷帕霉素靶蛋白(mTOR)、核糖体蛋白S6激酶(S6K)和核因子κB(NFκB)都参与了衰老过程。这一点很值得注意,因为这些相同的信号分子、癌蛋白和肿瘤抑制因子,都是癌症治疗中众所周知的靶点。此外,针对其中一些靶点的抗癌药物已经研发出来。鉴于癌症和衰老涉及相似的信号分子,这一药物库有可能用于抗衰老干预。在癌症中,癌细胞的内在和获得性耐药、肿瘤异质性、适应性和基因不稳定性都会阻碍癌症导向治疗。但对于抗衰老应用来说,这些障碍并不相关。例如,由于抗衰老干预应针对正常的有丝分裂后细胞,预计不会出现耐药性选择。在低剂量下,某些药物可能会减缓衰老和与年龄相关的疾病。重要的是,衰老的减缓反过来又可以推迟癌症,癌症是一种与年龄相关的疾病。

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