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Open AccessJournal ArticleDOI

Heterogeneity of cancer-associated fibroblasts: Opportunities for precision medicine.

Ryu Kanzaki, +1 more
- 11 Jul 2020 - 
- Vol. 111, Iss: 8, pp 2708-2717
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TLDR
Application of newly developed approaches to single‐cell analysis has already made an impact on understanding of the heterogeneity of cancer‐associated fibroblasts and the possibility of novel therapies targeting CAF subsets is discussed.
Abstract
Despite marked development in cancer therapies during recent decades, the prognosis for advanced cancer remains poor The conventional tumor-cell-centric view of cancer can only explain part of cancer progression, and thus a thorough understanding of the tumor microenvironment (TME) is crucial Among cells within the TME, cancer-associated fibroblasts (CAFs) are attracting attention as a target for cancer therapy However, CAFs present a heterogeneous population of cells and more detailed classification of CAFs and investigation of functions of each subset is needed to develop novel CAF-targeted therapies In this context, application of newly developed approaches to single-cell analysis has already made an impact on our understanding of the heterogeneity of CAFs Here, we review the recent literature on CAF heterogeneity and function, and discuss the possibility of novel therapies targeting CAF subsets

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Journal ArticleDOI

Clinical and therapeutic relevance of cancer-associated fibroblasts.

TL;DR: In this paper, the clinical relevance of CAFs is summarized with an emphasis on their value as prognosis factors and therapeutic targets, including how these complex bimodal functions evolve and are subjugated by neoplastic cells.
Journal ArticleDOI

Signaling pathways in cancer-associated fibroblasts and targeted therapy for cancer

TL;DR: In this paper, a comprehensive understanding of these signaling cascades in interactions between cancer cells and CAFs is necessary to fully realize the pivotal roles of CAFs in cancers, and three potential targeting strategies, including, epithelial-mesenchymal common targets, sequential target perturbation, and crosstalk-directed signaling targets, paving the way for CAF-directed or host cell-directed antitumor therapy.
Journal ArticleDOI

Targeting TGFβ signal transduction for cancer therapy.

TL;DR: A review of the role of transforming growth factor-β (TGFβ) in cancer initiation and progression is presented in this article, which summarizes the recent clinical advancements regarding TGFβ signaling interventions for cancer treatment, and discuss the remaining challenges and opportunities related to targeting this pathway.
Journal ArticleDOI

Cancer associated-fibroblast-derived exosomes in cancer progression.

TL;DR: In this article, the role of exosomes in the communication between CAFs and cancer cells and other cells of the TME is discussed, and the authors elaborate on the mechanisms by which CAFs-derived exosome contribute to cancer progression.
Journal ArticleDOI

CAFs Interacting With TAMs in Tumor Microenvironment to Enhance Tumorigenesis and Immune Evasion

TL;DR: In this paper, the authors summarized the distinct mechanisms about the complex interplay between CAFs and TAMs and highlighted the consequences of such a mutual relationship especially for tumor progression and tumor immune evasion, focusing on the synergistic pleiotropic effects.
References
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Journal ArticleDOI

The hallmarks of cancer.

TL;DR: This work has been supported by the Department of the Army and the National Institutes of Health, and the author acknowledges the support and encouragement of the National Cancer Institute.
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mRNA-Seq whole-transcriptome analysis of a single cell.

TL;DR: A single-cell digital gene expression profiling assay with only a single mouse blastomere is described, which detected the expression of 75% more genes than microarray techniques and identified 1,753 previously unknown splice junctions called by at least 5 reads.
Journal ArticleDOI

Tumour evolution inferred by single-cell sequencing

TL;DR: It is shown that with flow-sorted nuclei, whole genome amplification and next generation sequencing the authors can accurately quantify genomic copy number within an individual nucleus and indicate that tumours grow by punctuated clonal expansions with few persistent intermediates.
Journal ArticleDOI

The Myofibroblast: One Function, Multiple Origins

TL;DR: A better knowledge of the molecular mechanisms conducive to the appearance of differentiated myofibroblasts in each pathological situation will be useful for the understanding of fibrosis development in different organs and the planning of strategies aiming at their prevention and therapy.
Journal ArticleDOI

Stromal gene expression predicts clinical outcome in breast cancer

TL;DR: Genes represented in the new stroma-derived prognostic predictor (SDPP) reveal the strong prognostic capacity of differential immune responses as well as angiogenic and hypoxic responses, highlighting the importance of stromal biology in tumor progression.
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