Implications of systemic dysfunction for the etiology of malignancy.
Implications of systemic dysfunction for the etiology of malignancy.
复制标题
DOI：
10.4137/grsb.s10943
复制
发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Ochs MF
中科院分区：
文献类型：
--
作者：
Knox SS;Ochs MF
目前的肿瘤治疗方法是用药物治疗取代一般的细胞毒性化疗，药物治疗使与癌症发生和进展相关的特定分子靶点失活。目的是限制细胞损伤的途径被认为是直接负责恶性肿瘤。它的基本假设是双重的：(1)个体途径是恶性肿瘤的原因；(2)治疗目标应该是破坏肿瘤或功能失调通路。然而，数据在多大程度上支持这些假设还没有得到直接解决。越来越多的证据表明，在大多数成人癌症中，系统性功能障碍先于特定遗传/分子通路的破坏，激酶抑制剂等靶向治疗可能成功治疗一个通路，同时对其他非靶向通路产生意想不到的改变。本文讨论(1)恶性肿瘤的系统基础；(2)更好地分析与高风险相关的癌前生物标志物，以便及早制定预防性生活方式改变，在肿瘤发生前恢复高风险的表观遗传变化；(3)早期肿瘤的治疗重点是通过加强机体的先天防御机制来恢复系统平衡；(4)建立更好的系统定量模型，以捕获足够的复杂性，以便在肿瘤进展的各个阶段进行预测。
The current approach to treatment in oncology is to replace the generally cytotoxic chemotherapies with pharmaceutical treatment which inactivates specific molecular targets associated with cancer development and progression. The goal is to limit cellular damage to pathways perceived to be directly responsible for the malignancy. Its underlying assumptions are twofold: (1) that individual pathways are the cause of malignancy; and (2) that the treatment objective should be destruction—either of the tumor or the dysfunctional pathway. However, the extent to which data actually support these assumptions has not been directly addressed. Accumulating evidence suggests that systemic dysfunction precedes the disruption of specific genetic/molecular pathways in most adult cancers and that targeted treatments such as kinase inhibitors may successfully treat one pathway while generating unintended changes to other, non-targeted pathways. This article discusses (1) the systemic basis of malignancy; (2) better profiling of pre-cancerous biomarkers associated with elevated risk so that preventive lifestyle modifications can be instituted early to revert high-risk epigenetic changes before tumors develop; (3) a treatment emphasis in early stage tumors that would target the restoration of systemic balance by strengthening the body’s innate defense mechanisms; and (4) establishing better quantitative models of systems to capture adequate complexity for predictability at all stages of tumor progression.