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文献精选 > 高引权威"肿瘤微环境"文献

Tumor microenvironment as a therapeutic target in cancer. ​

文献信息 ​

DOI10.1016/j.pharmthera.2020.107753
PMID33259885
期刊Pharmacology & therapeutics
影响因子12.5
JCR 分区Q1
发表年份2021
被引次数946
关键词药物, 耐药性, 靶向治疗, 肿瘤微环境
文献类型Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review
ISSN0163-7258
页码107753
期号221()
作者Yi Xiao, Dihua Yu

一句话小结 ​

本研究探讨了肿瘤微环境在肿瘤发生、发展和治疗反应中的关键作用，强调了将其作为癌症治疗靶点的潜力与挑战。通过总结药物开发和临床试验的进展，提出了新技术和干预策略，以期提高治疗效果和克服现有障碍。

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药物 · 耐药性 · 靶向治疗 · 肿瘤微环境

摘要 ​

肿瘤微环境是指肿瘤中存在的非癌细胞及其组成部分，包括这些细胞所产生和释放的分子。肿瘤细胞与肿瘤微环境之间的持续相互作用在肿瘤的发生、进展、转移以及对治疗的反应中发挥了决定性作用。将肿瘤微环境作为癌症的治疗靶点已引起广泛的研究和临床关注。在此，我们总结了在药物开发和临床试验中针对肿瘤微环境的当前进展；强调了在针对肿瘤微环境以实现治疗效果方面所面临的挑战；探讨了更好地解析肿瘤微环境的新技术和方法；并讨论了干预促肿瘤微环境和最大化治疗收益的策略。

英文摘要 ​

Tumor microenvironment denotes the non-cancerous cells and components presented in the tumor, including molecules produced and released by them. The constant interactions between tumor cells and the tumor microenvironment play decisive roles in tumor initiation, progression, metastasis, and response to therapies. The tumor microenvironment as a therapeutic target in cancer has attracted great research and clinical interest. Here we summarize the current progress in targeting the tumor microenvironment in both drug development and clinical trials; highlight challenges in targeting the tumor microenvironment to achieve therapeutic efficacy; explore new technologies and approaches to better decipher the tumor microenvironment; and discuss strategies to intervene in the pro-tumor microenvironment and maximize therapeutic benefits.

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主要研究问题 ​

  1. 如何评估肿瘤微环境中不同细胞类型对肿瘤治疗反应的影响？
  2. 在针对肿瘤微环境的药物开发中，存在哪些主要的技术挑战？
  3. 当前有哪些新兴技术可以更有效地解析肿瘤微环境的复杂性？
  4. 肿瘤微环境的干预策略如何影响不同类型癌症的治疗效果？
  5. 未来的临床试验中，如何设计以评估肿瘤微环境作为治疗靶点的有效性？

核心洞察 ​

研究背景和目的 ​

肿瘤微环境（TME）是指肿瘤中存在的非癌细胞及其产生和释放的分子。肿瘤细胞与TME之间的相互作用在肿瘤的发生、发展、转移及对治疗的反应中起着决定性作用。本文旨在总结肿瘤微环境作为治疗靶点的最新进展，探讨在药物开发和临床试验中针对TME的策略，以及面临的挑战和未来方向。

主要方法/材料/实验设计 ​

本研究通过文献回顾和数据分析，综合了针对TME的各种药物开发和临床试验的进展。以下是研究的技术路线图：

Mermaid diagram

关键结果和发现 ​

  1. 癌相关成纤维细胞（CAFs）：

    • CAFs在肿瘤进展和耐药性中发挥重要作用。
    • 研究表明，CAFs通过分泌细胞因子和重塑ECM促进肿瘤细胞的侵袭和转移。

  2. 肿瘤相关巨噬细胞（TAMs）：

    • TAMs在肿瘤微环境中促进炎症、免疫逃逸和血管生成。
    • 针对TAMs的治疗策略显示出一定的潜力，但临床效果尚不明确。

  3. 肿瘤相关中性粒细胞（TANs）：

    • TANs通过分泌促炎因子和抑制性因子影响肿瘤进展。
    • 抗CXCR2的治疗策略正在开发中。

  4. 慢性炎症与血管生成：

    • 靶向促炎因子（如IL-1、TNF）和血管生成途径（如VEGF）在临床试验中显示出一定的前景。

主要结论/意义/创新性 ​

TME作为癌症治疗的新靶点，提供了潜在的治疗机会。尽管已有多种针对TME的治疗策略进入临床试验，但许多策略的疗效仍然有限，主要由于TME的复杂性和异质性。未来的研究需要深入了解TME的动态变化及其对治疗反应的影响，以便设计更有效的靶向治疗。

研究局限性和未来方向 ​

  1. 复杂性与异质性：TME中的细胞和非细胞成分存在高度的异质性，使得靶向治疗的设计变得复杂。
  2. 生物标志物的缺乏：缺乏有效的生物标志物来指导TME靶向治疗的临床应用。
  3. 未来方向：
    • 结合单细胞组学和人工智能技术，以更好地理解TME的复杂性。
    • 开发新的组合疗法，结合靶向TME的策略与其他治疗手段，以提高治疗效果。

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  2. Application of Nano-Drug Delivery System Based on Cascade Technology in Cancer Treatment. - Ying Sun;Xiaoli Ma;Hao Hu - International journal of molecular sciences (2021)
  3. Tumor-Associated Macrophages: A Potential Target for Cancer Therapy. - Yifan Tan;Min Wang;Yang Zhang;Shengyang Ge;Fan Zhong;Guowei Xia;Chuanyu Sun - Frontiers in oncology (2021)
  4. Nanoparticle-Mediated Targeted Drug Delivery to Remodel Tumor Microenvironment for Cancer Therapy. - Lu Tang;Yijun Mei;Yan Shen;Shun He;Qiaqia Xiao;Yue Yin;Yonggang Xu;Jie Shao;Wei Wang;Zihao Cai - International journal of nanomedicine (2021)
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