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MicroRNAs and the cellular response to rapamycin Potential role in diagnosis and therapy

机译:MicroRNA和细胞对雷帕霉素的反应在诊断和治疗中的潜在作用

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摘要

The mammalian target of rapamycin (mTOR) is a major regulator of cell growth, motility and angiogenesis that is often deregulated in malignancies. mTOR inhibitors have been approved for the treatment of renal cell carcinoma and mantle cell lymphoma. Currently, second-generation mTOR inhibitors are under clinical evaluation. Major challenges remain in the identification of patients who will respond to mTOR inhibitors and the development of therapeutics that can overcome intrinsic resistance or acquired resistance. There are currently no bio-markers that predict tumor response to mTOR inhibitors.MicroRNAs (miRNAs) are endogenous small non-coding RNAs that regulate gene expression. MiRNAs participate in many biological processes, including proliferation and apoptosis. MiRNAs are often deregulated in cancer and act as tumor suppressors or oncogenes. Recently miRNAs emerged as diagnostic and prognostic markers to assess therapeutic responses, giving rise to the field of miRNA pharmacogenomics. Numerous studies indicate that mTOR and its signaling pathway is regulated by miRNAs. However, little is known as to whether miRNAs play a role in the intrinsic tumor resistance or the development of acquired resistance to mTOR inhibitors.
机译:雷帕霉素(mTOR)的哺乳动物靶标是细胞生长,运动和血管生成的主要调节剂,通常在恶性肿瘤中被解除调节。 mTOR抑制剂已被批准用于治疗肾细胞癌和套细胞淋巴瘤。当前,第二代mTOR抑制剂正在临床评估中。在鉴定对mTOR抑制剂有反应的患者以及开发可以克服内在抗性或获得性抗性的疗法方面,主要挑战仍然存在。目前尚无可预测肿瘤对mTOR抑制剂反应的生物标志物。MicroRNA(miRNA)是调节基因表达的内源性小非编码RNA。 MiRNA参与许多生物学过程,包括增殖和凋亡。 MiRNA通常在癌症中被解除调节,并充当肿瘤抑制因子或致癌基因。最近,miRNAs作为评估治疗反应的诊断和预后标志物出现,从而引起了miRNA药物基因组学领域的发展。大量研究表明,mTOR及其信号传导途径受miRNA调控。然而,关于miRNA是否在固有的肿瘤抗性或对mTOR抑制剂的获得性抗性的发展中发挥作用,鲜为人知。

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