Martín-Lorenzo Alberto, Gonzalez-Herrero Inés, Rodríguez-Hernández Guillermo, García-Ramírez Idoia, Vicente-Dueñas Carolina, Sánchez-García Isidro
Biol Chem. 2014 Nov 1;395(11):1315-20. doi: 10.1515/hsz-2014-0185.
Abstract A cancer dogma states that inactivation of oncogene(s) can cause cancer remission, implying that oncogenes are the Achilles' heel of cancers. This current model of cancer has kept oncogenes firmly in focus as therapeutic targets and is in agreement with the fact that in human cancers all cancerous cells, with independence of the cellular heterogeneity existing within the tumour, carry the same oncogenic genetic lesions. However, recent studies of the interactions between an oncogene and its target cell have shown that oncogenes contribute to cancer development via developmental reprogramming of the epigenome within the target cell. These results provide the first evidence that carcinogenesis can be initiated by epigenetic stem cell reprogramming, and uncover a new role for oncogenes in the origin of cancer. Here we analyse these evidences and discuss how this vision offers new avenues for developing novel anti-cancer interventions.
摘要 一种癌症理论认为,癌基因失活可导致癌症缓解,这意味着癌基因是癌症的致命弱点。当前的这种癌症模型一直将癌基因作为治疗靶点予以密切关注,这与以下事实相符:在人类癌症中,所有癌细胞,无论肿瘤内存在的细胞异质性如何,都携带相同的致癌基因损伤。然而,最近关于癌基因与其靶细胞相互作用的研究表明,癌基因通过对靶细胞内表观基因组进行发育重编程来促进癌症发展。这些结果首次证明致癌作用可由表观遗传干细胞重编程引发,并揭示了癌基因在癌症起源中的新作用。在此,我们分析这些证据,并讨论这一观点如何为开发新型抗癌干预措施提供新途径。