适应和学习分子网络作为系统水平癌症发展的描述：在抗癌治疗中的潜在用途
Adaptation and learning of molecular networks as a description of cancer development at the systems-level: Potential use in anti-cancer therapies
摘要：
人们越来越认识到癌细胞是复杂发育过程的产物。癌的发生和转移越来越多地被描述为系统水平的网络现象。在这里，我们提出，恶性转化是一个两阶段的过程，在最初的系统可塑性增加，其次是可塑性下降，在晚期阶段的癌变作为一个模型的细胞学习。我们描述了早期肿瘤起始细胞的系统可塑性增加的标志，例如增加的噪声、熵、构象和表型可塑性、物理变形性、细胞异质性和网络重排。最后，我们认为，在癌症发展过程中的分子网络的大的结构变化，需要一个相当不同的靶向策略，在早期和晚期阶段的癌。早期癌症发展的可塑性网络需要中心打击，而晚期原发性肿瘤或已建立的转移的刚性网络应通过网络影响策略进行攻击，例如通过边缘，多靶点或异网络药物。癌症干细胞需要特殊的诊断和靶向，因为它们的休眠和快速增殖形式可能分别具有更刚性或更可塑的网络。改变其刚性/可塑性的极高能力可能是癌症干细胞的关键分化标志。将早期优化的抗癌药物应用于晚期患者可能是许多抗癌治疗失败的原因。我们在这里提出的假设是基于对患者特异性多靶点治疗的需求，该治疗以优化的顺序应用中心命中和网络影响的正确比例。
英文摘要：
There is a widening recognition that cancer cells are products of complex developmental processes. Carcinogenesis and metastasis formation are increasingly described as systems-level, network phenomena. Here we propose that malignant transformation is a two-phase process, where an initial increase of system plasticity is followed by a decrease of plasticity at late stages of carcinogenesis as a model of cellular learning. We describe the hallmarks of increased system plasticity of early, tumor initiating cells, such as increased noise, entropy, conformational and phenotypic plasticity, physical deformability, cell heterogeneity and network rearrangements. Finally, we argue that the large structural changes of molecular networks during cancer development necessitate a rather different targeting strategy in early and late phase of carcinogenesis. Plastic networks of early phase cancer development need a central hit, while rigid networks of late stage primary tumors or established metastases should be attacked by the network influence strategy, such as by edgetic, multi-target, or allo-network drugs. Cancer stem cells need special diagnosis and targeting, since their dormant and rapidly proliferating forms may have more rigid, or more plastic networks, respectively. The extremely high ability to change their rigidity/plasticity may be a key differentiating hallmark of cancer stem cells. The application of early stage-optimized anti-cancer drugs to late-stage patients may be a reason of many failures in anti-cancer therapies. Our hypotheses presented here underlie the need for patient-specific multi-target therapies applying the correct ratio of central hits and network influences -- in an optimized sequence.
机构、总结、中文摘要均由AI分析而来，可能存在错误，请以论文正文为准。
