Recent progress in fungus-derived bioactive agents for targeting of signaling machinery in cancer cells.
Recent progress in fungus-derived bioactive agents for targeting of signaling machinery in cancer cells.
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DOI：
10.2147/dddt.s77341
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Ismail M
中科院分区：
文献类型：
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作者：
Lin X;Farooqi AA;Ismail M
越来越多的人认识到，肿瘤细胞可能具有不同的突变，并依赖于不同的细胞内信号级联以实现存活或转移潜力。癌基因的过表达、肿瘤抑制基因的失活、遗传/表观遗传突变、基因组不稳定性和凋亡细胞死亡的丧失是分子肿瘤学中已被广泛研究的一些机制。我们将这一多组分综述划分为从体外和异种移植模型中获得的真菌物质抗癌活性的最新证据，这些真菌物质调节致癌和抑癌miRNA的表达。在不同的癌细胞系和临床前模型中，关于真菌衍生的化学诱导的细胞内信号网络的调节存在一些突出的问题。已经出现了某些提示，强调了凋亡可以在TRAIL抗性癌细胞中恢复的机制。从这些新兴研究领域获得的知识的重新认识将使我们能够潜在地识别具有显著抗癌活性和最小脱靶效应的天然药物。将从癌细胞系基因表达中获得的实验验证证据与大规模功能筛选结果和药理学敏感性数据相结合，将有助于鉴定具有显著疗效的治疗剂。新的工具和技术将进一步加深我们对信号网络的理解，这些信号网络是癌症发展，转移和对个人和系统范围内不同疗法的耐药性的基础。
It is becoming increasingly understood that tumor cells may have different mutations and dependencies on diverse intracellular signaling cascades for survival or metastatic potential. Overexpression of oncogenes, inactivation of tumor suppressor genes, genetic/epigenetic mutations, genomic instability, and loss of apoptotic cell death are some of the mechanisms that have been widely investigated in molecular oncology. We partition this multicomponent review into the most recent evidence on the anticancer activity of fungal substances obtained from in vitro and xenografted models, and these fungal substances modulate expression of oncogenic and tumor suppressor miRNAs. There are some outstanding questions regarding fungus-derived chemical-induced modulation of intracellular signaling networks in different cancer cell lines and preclinical models. Certain hints have emerged, emphasizing mechanisms via which apoptosis can be restored in TRAIL-resistant cancer cells. Reconceptualization of the knowledge obtained from these emerging areas of research will enable us to potentially identify natural agents with notable anticancer activity and minimal off-target effects. Integration of experimentally verified evidence obtained from cancer cell line gene expression with large-scale functional screening results and pharmacological sensitivity data will be helpful in identification of therapeutics with substantial efficacy. New tools and technologies will further deepen our understanding of the signaling networks that underlie the development of cancer, metastasis, and resistance to different therapeutics at both a personal and systems-wide level.