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Curated Papers > High-impact authoritative literature on "tumor microenvironment"

Tumor microenvironment as a therapeutic target in cancer. ​

Literature Information ​

DOI10.1016/j.pharmthera.2020.107753
PMID33259885
JournalPharmacology & therapeutics
Impact Factor12.5
JCR QuartileQ1
Publication Year2021
Times Cited946
KeywordsDrug, Resistance, Target, Therapy, Tumor microenvironment
Literature TypeJournal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review
ISSN0163-7258
Pages107753
Issue221()
AuthorsYi Xiao, Dihua Yu

TL;DR ​

This paper reviews the critical role of the tumor microenvironment in cancer progression and treatment response, emphasizing its potential as a therapeutic target. It highlights recent advancements in drug development and clinical trials, while addressing the challenges and new approaches to effectively manipulate the tumor microenvironment for improved therapeutic outcomes.

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Drug · Resistance · Target · Therapy · Tumor microenvironment

Abstract ​

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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Primary Questions Addressed ​

  1. What specific components of the tumor microenvironment are currently being targeted in therapeutic strategies?
  2. How do different tumor microenvironments affect the efficacy of various cancer therapies?
  3. What are the most promising new technologies for analyzing the tumor microenvironment in research and clinical settings?
  4. How can the pro-tumor microenvironment be effectively modified to enhance the response to existing cancer treatments?
  5. What challenges have researchers encountered in translating findings about the tumor microenvironment into successful clinical applications?

Key Findings ​

Research Background and Objectives ​

The tumor microenvironment (TME) comprises non-cancerous cells and components surrounding tumor cells, including immune cells, fibroblasts, and extracellular matrix (ECM). The interactions between tumor cells and the TME are critical for tumor progression, metastasis, and treatment response. This review aims to summarize the current advancements in targeting the TME for cancer therapy, highlight challenges, and explore innovative technologies and strategies to enhance therapeutic efficacy.

Main Methods/Materials/Experimental Design ​

The review discusses various strategies for targeting components of the TME, including:

  1. Targeting Tumor-Infiltrating T-Cells: Enhancing anti-tumor immunity.
  2. Targeting Cancer-Associated Fibroblasts (CAFs): Involved in tumor progression and drug resistance.
  3. Targeting Tumor-Associated Macrophages (TAMs): Linked to poor clinical outcomes.
  4. Targeting Neutrophils: Their role in promoting tumor progression.
  5. Targeting Chronic Inflammation: A hallmark of cancer that supports tumor growth.
  6. Targeting Angiogenesis: Essential for tumor development.

The review employs a structured approach, summarizing drug development efforts targeting these components and discussing the complexity and dynamic nature of the TME.

Mermaid diagram

Key Results and Findings ​

  • CAFs: Found to be crucial in promoting tumor growth and drug resistance. Various drugs targeting CAFs, including FAP-targeting immunotoxins, are in clinical trials.
  • TAMs: Show a strong correlation with tumor progression and therapy resistance. CSF1R inhibitors are being explored for their ability to deplete TAMs.
  • Neutrophils: Their role as pro-tumor entities is highlighted, with CXCR2 inhibitors showing promise in preclinical studies.
  • Chronic Inflammation: Anti-inflammatory drugs have shown potential in reducing cancer risks.
  • Angiogenesis: Anti-VEGF therapies have shown limited efficacy, suggesting the need for combination strategies.

Main Conclusions/Significance/Innovation ​

The TME is a critical target for cancer therapy due to its complex interactions with tumor cells. Effective strategies must consider the heterogeneous and dynamic nature of the TME. Targeting specific components of the TME may enhance therapeutic efficacy and overcome resistance mechanisms. The integration of novel technologies such as single-cell sequencing and AI in TME research holds promise for developing more effective cancer therapies.

Research Limitations and Future Directions ​

  • Limitations: Many clinical trials targeting the TME have failed, often due to the complexity of the TME and the paradoxical roles of its components (e.g., some CAFs may have tumor-suppressive functions).
  • Future Directions: Emphasis on biomarker-guided therapies, combinatorial approaches, and further understanding of the TME's cellular and molecular dynamics is essential. Continued exploration of novel therapeutic strategies that reprogram the TME rather than merely depleting its components may lead to improved patient outcomes.

In summary, the TME represents a promising avenue for cancer therapy, necessitating a deeper understanding of its complexities and interactions with tumor cells to develop effective treatments.

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Literatures Citing This Work ​

  1. Identification of a prognostic and therapeutic immune signature associated with hepatocellular carcinoma. - Yanan Peng;Chang Liu;Mengting Li;Wenjie Li;Mengna Zhang;Xiang Jiang;Ying Chang;Lan Liu;Fan Wang;Qiu Zhao - Cancer cell international (2021)
  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)
  5. Development of a seven-gene tumor immune microenvironment prognostic signature for high-risk grade III endometrial cancer. - Mingjun Zheng;Yuexin Hu;Rui Gou;Siting Li;Xin Nie;Xiao Li;Bei Lin - Molecular therapy oncolytics (2021)
  6. Integrated bioinformatics analyses of key genes involved in hepatocellular carcinoma immunosuppression. - Hongyan Huang;Youwen Hu;Li Guo;Zhili Wen - Oncology letters (2021)
  7. Mesenchymal Stem Cells With Cancer-Associated Fibroblast-Like Phenotype Stimulate SDF-1/CXCR4 Axis to Enhance the Growth and Invasion of B-Cell Acute Lymphoblastic Leukemia Cells Through Cell-to-Cell Communication. - Chengyun Pan;Qin Fang;Ping Liu;Dan Ma;Shuyun Cao;Luxin Zhang;Qingzhen Chen;Tianzhen Hu;Jishi Wang - Frontiers in cell and developmental biology (2021)
  8. LncRNA FOXP4-AS1 Promotes Progression of Ewing Sarcoma and Is Associated With Immune Infiltrates. - Jiachao Xiong;Liang Wu;Lu Huang;Chunyang Wu;Zhiming Liu;Wenqiang Deng;Shengbiao Ma;Zhenhai Zhou;Honggui Yu;Kai Cao - Frontiers in oncology (2021)
  9. Exosomal circRNAs: Emerging Players in Tumor Metastasis. - Hao Zhou;Xiaoyun He;Yuxiang He;Chunlin Ou;Pengfei Cao - Frontiers in cell and developmental biology (2021)
  10. The potential role of exosomal circRNAs in the tumor microenvironment: insights into cancer diagnosis and therapy. - Juan Li;Guo Zhang;Chen-Guang Liu;Xiaoqiang Xiang;Minh T N Le;Gautam Sethi;Lingzhi Wang;Boon-Cher Goh;Zhaowu Ma - Theranostics (2022)

... (936 more literatures)

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