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致癌和抑癌通路:癌症治疗的机遇与挑战。

Pro-oncogenic and anti-oncogenic pathways: opportunities and challenges of cancer therapy.

机构信息

Department of Anatomy & Cell Biology, The Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA.

出版信息

Future Oncol. 2010 Apr;6(4):587-603. doi: 10.2217/fon.10.15.

Abstract

Carcinogenesis is the uncontrolled growth of cells gaining the potential to invade and disrupt vital tissue functions. This malignant process includes the occurrence of 'unwanted' gene mutations that induce the transformation of normal cells, for example, by overactivation of pro-oncogenic pathways and inactivation of tumor-suppressive or anti-oncogenic pathways. It is now recognized that the number of major signaling pathways that control oncogenesis is not unlimited; therefore, suppressing these pathways can conceivably lead to a cancer cure. However, the clinical application of cancer intervention has not matched up to scientific expectations. Increasing numbers of studies have revealed that many oncogenic-signaling elements show double faces, in which they can promote or suppress cancer pathogenesis depending on tissue type, cancer stage, gene dosage and their interaction with other players in carcinogenesis. This complexity of oncogenic signaling poses challenges to traditional cancer therapy and calls for considerable caution when designing an anticancer drug strategy. We propose future oncology interventions with the concept of integrative cancer therapy.

摘要

致癌作用是细胞的失控生长,这些细胞具有侵袭和破坏重要组织功能的潜力。这个恶性过程包括“不需要的”基因突变的发生,这些基因突变诱导正常细胞的转化,例如通过原癌基因途径的过度激活和肿瘤抑制或抑癌途径的失活。现在人们认识到,控制致癌作用的主要信号通路的数量并不是无限的;因此,抑制这些通路可能可以导致癌症治愈。然而,癌症干预的临床应用并没有达到科学预期。越来越多的研究表明,许多致癌信号元件具有双重作用,它们可以根据组织类型、癌症阶段、基因剂量以及它们与致癌作用中其他参与者的相互作用,促进或抑制癌症的发病机制。致癌信号的这种复杂性给传统的癌症治疗带来了挑战,在设计抗癌药物策略时需要非常谨慎。我们提出了未来肿瘤学干预的综合癌症治疗概念。

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