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Therapeutic Targeting of the Tumor Microenvironment.
Literature Information
| DOI | 10.1158/2159-8290.CD-20-1808 |
|---|---|
| PMID | 33811125 |
| Journal | Cancer discovery |
| Impact Factor | 33.3 |
| JCR Quartile | Q1 |
| Publication Year | 2021 |
| Times Cited | 801 |
| Keywords | tumor microenvironment, cancer treatment, immunotherapy, antiangiogenic drugs, cancer-associated fibroblasts |
| Literature Type | Journal Article, Research Support, Non-U.S. Gov't, Review |
| ISSN | 2159-8274 |
| Pages | 933-959 |
| Issue | 11(4) |
| Authors | Leire Bejarano, Marta J C Jordāo, Johanna A Joyce |
TL;DR
This review discusses the emerging strategies for targeting the tumor microenvironment (TME) in cancer treatment, focusing on advanced therapies such as immunotherapies and antiangiogenic drugs that are either approved or under clinical evaluation. It highlights the significance of understanding the TME's role in tumor progression and treatment response, while addressing the challenges and future directions in this rapidly evolving area of cancer research.
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tumor microenvironment · cancer treatment · immunotherapy · antiangiogenic drugs · cancer-associated fibroblasts
Abstract
Strategies to therapeutically target the tumor microenvironment (TME) have emerged as a promising approach for cancer treatment in recent years due to the critical roles of the TME in regulating tumor progression and modulating response to standard-of-care therapies. Here, we summarize the current knowledge regarding the most advanced TME-directed therapies, which have either been clinically approved or are currently being evaluated in trials, including immunotherapies, antiangiogenic drugs, and treatments directed against cancer-associated fibroblasts and the extracellular matrix. We also discuss some of the challenges associated with TME therapies, and future perspectives in this evolving field. SIGNIFICANCE: This review provides a comprehensive analysis of the current therapies targeting the TME, combining a discussion of the underlying basic biology with clinical evaluation of different therapeutic approaches, and highlighting the challenges and future perspectives.
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Primary Questions Addressed
- What are the most promising immunotherapies currently being evaluated for targeting the tumor microenvironment?
- How do cancer-associated fibroblasts influence the effectiveness of standard cancer treatments in the context of the tumor microenvironment?
- What specific challenges do researchers face when developing therapies aimed at the extracellular matrix within the tumor microenvironment?
- In what ways can antiangiogenic drugs be combined with other therapies to enhance treatment outcomes in cancer patients?
- How does the tumor microenvironment differ across various cancer types, and what implications does this have for therapeutic targeting strategies?
Key Findings
1. Research Background and Purpose: The tumor microenvironment (TME) plays a pivotal role in cancer progression and influences how tumors respond to conventional therapies. Recognizing these dynamics, researchers have focused on therapeutic strategies that specifically target the TME as a novel approach to enhance cancer treatment efficacy. The purpose of this review is to summarize the current advancements in TME-targeted therapies, including those that have gained clinical approval and those still under trial, while also addressing the challenges and future directions in this rapidly evolving area of cancer treatment.
2. Main Methods and Findings: The review systematically compiles and analyzes the various TME-directed therapies currently available or in development. These include:
- Immunotherapies: These harness the immune system to attack cancer cells, with the TME influencing immune cell infiltration and activity.
- Antiangiogenic Drugs: These aim to disrupt blood vessel formation within tumors, which is crucial for tumor growth and metastasis.
- Treatments Targeting Cancer-Associated Fibroblasts: These therapies focus on modifying the fibroblasts that contribute to the supportive stroma of the tumor, thus altering the TME.
- Extracellular Matrix Modulators: These treatments target the matrix that surrounds tumor cells, affecting cell behavior and tumor progression.
The review highlights the clinical outcomes of these therapies, noting successes and ongoing clinical trials that provide insights into their effectiveness and safety.
3. Core Conclusion: The targeting of the TME presents a promising avenue for improving cancer therapy outcomes. While several approaches have shown clinical efficacy, there remain significant challenges, including tumor heterogeneity, the complex interplay between tumor cells and the TME, and the need for better biomarkers to predict therapeutic response. It is crucial to integrate an understanding of TME biology into therapeutic design to overcome current limitations.
4. Research Significance and Impact: This review emphasizes the significance of TME-targeted therapies in the context of modern oncology, illustrating their potential to complement existing treatments and improve patient outcomes. By combining insights from basic biology with clinical applications, the review sheds light on a transformative approach that could lead to more personalized and effective cancer treatments. The discussion of challenges and future perspectives serves to guide ongoing research efforts, ultimately aiming to enhance the therapeutic landscape for cancer patients.
Literatures Citing This Work
- Cancer‑associated fibroblast‑induced M2‑polarized macrophages promote hepatocellular carcinoma progression via the plasminogen activator inhibitor‑1 pathway. - Shuhai Chen;Yuji Morine;Kazunori Tokuda;Shinichiro Yamada;Yu Saito;Masaaki Nishi;Tetsuya Ikemoto;Mitsuo Shimada - International journal of oncology (2021)
- Stimuli-Responsive Polymeric Nanoplatforms for Cancer Therapy. - Di Chang;Yuanyuan Ma;Xiaoxuan Xu;Jinbing Xie;Shenghong Ju - Frontiers in bioengineering and biotechnology (2021)
- Circadian regulation of cancer cell and tumor microenvironment crosstalk. - Wenjing Xuan;Fatima Khan;Charles David James;Amy B Heimberger;Maciej S Lesniak;Peiwen Chen - Trends in cell biology (2021)
- Cancer-associated fibroblast infiltration in gastric cancer: the discrepancy in subtypes pathways and immunosuppression. - Xu Liu;Li Yao;Jingkun Qu;Lin Liu;Ning Lu;Jiansheng Wang;Jia Zhang - Journal of translational medicine (2021)
- Endogenous and Therapeutic Estrogens: Maestro Conductors of the Microenvironment of ER+ Breast Cancers. - Linda A Schuler;Fern E Murdoch - Cancers (2021)
- Targeting the tumor microenvironment in B-cell lymphoma: challenges and opportunities. - Yingyue Liu;Xiangxiang Zhou;Xin Wang - Journal of hematology & oncology (2021)
- Nanocarriers Used in Drug Delivery to Enhance Immune System in Cancer Therapy. - Giovanna C N B Lôbo;Karen L R Paiva;Ana Luísa G Silva;Marina M Simões;Marina A Radicchi;Sônia N Báo - Pharmaceutics (2021)
- Apoptosis Deregulation and the Development of Cancer Multi-Drug Resistance. - Christiana M Neophytou;Ioannis P Trougakos;Nuray Erin;Panagiotis Papageorgis - Cancers (2021)
- 3D Model of the Early Melanoma Microenvironment Captures Macrophage Transition into a Tumor-Promoting Phenotype. - Gabriela A Pizzurro;Chang Liu;Kathryn Bridges;Amanda F Alexander;Alice Huang;Janani P Baskaran;Julie Ramseier;Marcus W Bosenberg;Michael Mak;Kathryn Miller-Jensen - Cancers (2021)
- In Situ Cancer Vaccination and Immunovirotherapy Using Oncolytic HSV. - Nusrat Jahan;Shanawaz M Ghouse;Robert L Martuza;Samuel D Rabkin - Viruses (2021)
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