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Tumor microenvironment and therapeutic response.
Literature Information
| DOI | 10.1016/j.canlet.2016.01.043 |
|---|---|
| PMID | 26845449 |
| Journal | Cancer letters |
| Impact Factor | 10.1 |
| JCR Quartile | Q1 |
| Publication Year | 2017 |
| Times Cited | 1033 |
| Keywords | Microenvironment, Resistance, Target therapy |
| Literature Type | Journal Article, Review, Research Support, Non-U.S. Gov't |
| ISSN | 0304-3835 |
| Pages | 61-68 |
| Issue | 387() |
| Authors | Ting Wu, Yun Dai |
TL;DR
This study highlights the critical role of the tumor microenvironment in influencing therapeutic responses and drug resistance, driven by factors such as soluble secretions and cell adhesion to stromal components. The findings suggest that developing targeted therapies that disrupt these interactions and reprogram immune responses may enhance treatment efficacy and address therapeutic resistance.
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Microenvironment · Resistance · Target therapy
Abstract
The tumor microenvironment significantly influences therapeutic response and clinical outcome. Microenvironment-mediated drug resistance can be induced by soluble factors secreted by tumor or stromal cells. The adhesion of tumor cells to stromal fibroblasts or to components of the extracellular matrix can also blunt therapeutic response. Microenvironment-targeted therapy strategies include inhibition of the extracellular ligand-receptor interactions and downstream pathways. Immune cells can both improve and obstruct therapeutic efficacy and may vary in their activation status within the tumor microenvironment; thus, re-programme of the immune response would be substantially more beneficial. The development of rational drug combinations that can simultaneously target tumor cells and the microenvironment may represent a solution to overcome therapeutic resistance.
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Primary Questions Addressed
- How do specific soluble factors in the tumor microenvironment contribute to drug resistance in different types of cancer?
- What are the most effective strategies for reprogramming immune responses within the tumor microenvironment to enhance therapeutic outcomes?
- How does the interaction between tumor cells and stromal fibroblasts affect the efficacy of current cancer therapies?
- In what ways can the inhibition of ligand-receptor interactions in the tumor microenvironment be optimized to improve patient responses to treatment?
- What are the challenges and opportunities in developing rational drug combinations that target both tumor cells and the surrounding microenvironment?
Key Findings
Key Insights
Research Background and Objectives
The tumor microenvironment (TME) plays a crucial role in determining therapeutic responses and clinical outcomes in cancer treatment. Understanding the interplay between tumor cells, stromal cells, immune cells, and extracellular matrix components is essential for developing effective therapies. The purpose of this research is to explore how the TME contributes to drug resistance and to identify potential strategies for enhancing therapeutic efficacy by targeting the interactions within the microenvironment.Major Methods and Findings
The study employs a comprehensive review of existing literature to analyze the multifaceted interactions between tumor cells and their microenvironment. It highlights that soluble factors released by tumor or stromal cells can induce drug resistance, while the adhesion of tumor cells to stromal fibroblasts or extracellular matrix components can diminish the effectiveness of treatments. The findings indicate that therapeutic strategies aimed at disrupting extracellular ligand-receptor interactions and their downstream signaling pathways can mitigate these adverse effects. Furthermore, the role of immune cells is emphasized, noting that their activation status can either enhance or hinder treatment efficacy, suggesting that reprogramming the immune response within the TME is critical for improving outcomes.Core Conclusions
The research concludes that the TME is a significant determinant of therapeutic response, with various components contributing to drug resistance. Effective interventions must consider both tumor cells and the surrounding microenvironment. The study advocates for the development of rational drug combinations that target the tumor directly while also addressing the supportive roles of the microenvironment. This dual approach may be necessary to overcome the challenges posed by microenvironment-mediated resistance.Research Significance and Impact
The insights gained from this research are pivotal for advancing cancer therapy. By recognizing the TME as a critical player in therapeutic outcomes, this work encourages a shift in focus towards microenvironment-targeted therapies. The implications are profound, as they suggest that improving treatment efficacy will require innovative strategies that simultaneously address the complexities of the TME and the tumor itself. This research could lead to more effective cancer treatments, ultimately improving patient survival rates and quality of life. The findings may also inspire further investigations into personalized medicine approaches that consider individual TME characteristics in treatment planning.
Literatures Citing This Work
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- Interleukin-17A promotes tongue squamous cell carcinoma metastasis through activating miR-23b/versican pathway. - Tai Wei;Xin Cong;Xiang-Ting Wang;Xiao-Jian Xu;Sai-Nan Min;Peng Ye;Xin Peng;Li-Ling Wu;Guang-Yan Yu - Oncotarget (2017)
- Teaming Up for Trouble: Cancer Cells, Transforming Growth Factor-β1 Signaling and the Epigenetic Corruption of Stromal Naïve Fibroblasts. - Sergio Lamprecht;Ina Sigal-Batikoff;Shraga Shany;Naim Abu-Freha;Eduard Ling;George J Delinasios;Keren Moyal-Atias;John G Delinasios;Alexander Fich - Cancers (2018)
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- Complex interplay between tumor microenvironment and cancer therapy. - Minhong Shen;Yibin Kang - Frontiers of medicine (2018)
- Low tumor purity is associated with poor prognosis, heavy mutation burden, and intense immune phenotype in colon cancer. - Yihao Mao;Qingyang Feng;Peng Zheng;Liangliang Yang;Tianyu Liu;Yuqiu Xu;Dexiang Zhu;Wenju Chang;Meiling Ji;Li Ren;Ye Wei;Guodong He;Jianmin Xu - Cancer management and research (2018)
- IL-17A promotes cell migration and invasion of glioblastoma cells via activation of PI3K/AKT signalling pathway. - Qianqian Zheng;Shuo Diao;Qi Wang;Chen Zhu;Xun Sun;Bo Yin;Xinwen Zhang;Xin Meng;Biao Wang - Journal of cellular and molecular medicine (2019)
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