A framework for advancing our understanding of cancer-associated fibroblasts

Nature reviews. Cancer, Journal Year: 2020, Volume and Issue: 20(3), P. 174 - 186

Published: Jan. 24, 2020

Abstract Cancer-associated fibroblasts (CAFs) are a key component of the tumour microenvironment with diverse functions, including matrix deposition and remodelling, extensive reciprocal signalling interactions cancer cells crosstalk infiltrating leukocytes. As such, they potential target for optimizing therapeutic strategies against cancer. However, many challenges present in ongoing attempts to modulate CAFs benefit. These include limitations our understanding origin heterogeneity CAF function, it being desirable retain some antitumorigenic functions. On basis meeting experts field biology, we summarize this Consensus Statement current knowledge framework advancing critical cell type within microenvironment.

Language: Английский

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Crosstalk between cancer-associated fibroblasts and immune cells in the tumor microenvironment: new findings and future perspectives

Molecular Cancer, Journal Year: 2021, Volume and Issue: 20(1)

Published: Oct. 11, 2021

Abstract Cancer-associated fibroblasts (CAFs), a stromal cell population with cell-of-origin, phenotypic and functional heterogeneity, are the most essential components of tumor microenvironment (TME). Through multiple pathways, activated CAFs can promote growth, angiogenesis, invasion metastasis, along extracellular matrix (ECM) remodeling even chemoresistance. Numerous previous studies have confirmed critical role interaction between cells in tumorigenesis development. However, recently, mutual effects immune (TIME) been identified as another key factor promoting progression. The TIME mainly consists distinct populations islets is highly associated antitumor immunological state TME. interact tumor-infiltrating well other within via secretion various cytokines, growth factors, chemokines, exosomes effector molecules, consequently shaping an immunosuppressive TME that enables cancer to evade surveillance system. In-depth interactions, particularly complicated mechanisms connecting cells, might provide novel strategies for subsequent targeted immunotherapies. Herein, we shed light on recent advances regarding direct indirect crosstalk infiltrating further summarize possible immunoinhibitory induced by In addition, present current related CAF-targeting immunotherapies briefly describe some future perspectives CAF research end.

Language: Английский

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Tumor microenvironment as a therapeutic target in cancer

Pharmacology & Therapeutics, Journal Year: 2020, Volume and Issue: 221, P. 107753 - 107753

Published: Nov. 28, 2020

Language: Английский

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The tumour microenvironment in pancreatic cancer — clinical challenges and opportunities

Nature Reviews Clinical Oncology, Journal Year: 2020, Volume and Issue: 17(9), P. 527 - 540

Published: May 12, 2020

Language: Английский

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Diversity and Biology of Cancer-Associated Fibroblasts

Physiological Reviews, Journal Year: 2020, Volume and Issue: 101(1), P. 147 - 176

Published: May 29, 2020

Efforts to develop anti-cancer therapies have largely focused on targeting the epithelial compartment, despite presence of non-neoplastic stromal components that substantially contribute progression tumor. Indeed, cancer cell survival, growth, migration, and even dormancy are influenced by surrounding tumor microenvironment (TME). Within TME, cancer-associated fibroblasts (CAFs) been shown play several roles in development a They secrete growth factors, inflammatory ligands, extracellular matrix proteins promote proliferation, therapy resistance, immune exclusion. However, recent work indicates CAFs may also restrain some circumstances. In this review, we summarize body CAFs, with particular focus most discoveries about fibroblast heterogeneity, plasticity, functions. We highlight commonalities present across different types, normal states. Finally, latest advances regarding therapeutic strategies undergoing preclinical clinical evaluation.

Language: Английский

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Targeting STAT3 in Cancer Immunotherapy

Molecular Cancer, Journal Year: 2020, Volume and Issue: 19(1)

Published: Sept. 24, 2020

Abstract As a point of convergence for numerous oncogenic signaling pathways, signal transducer and activator transcription 3 (STAT3) is central in regulating the anti-tumor immune response. STAT3 broadly hyperactivated both cancer non-cancerous cells within tumor ecosystem plays important roles inhibiting expression crucial activation regulators promoting production immunosuppressive factors. Therefore, targeting pathway has emerged as promising therapeutic strategy cancers. In this review, we outline importance tumorigenesis its regulation, highlight current status development STAT3-targeting approaches. We also summarize discuss recent advances STAT3-based combination immunotherapy detail. These endeavors provide new insights into translational application may contribute to promotion more effective treatments toward malignancies.

Language: Английский

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Cancer-associated fibroblasts: an emerging target of anti-cancer immunotherapy

Journal of Hematology & Oncology, Journal Year: 2019, Volume and Issue: 12(1)

Published: Aug. 28, 2019

Among all the stromal cells that present in tumor microenvironment, cancer-associated fibroblasts (CAFs) are one of most abundant and critical components mesenchyme, which not only provide physical support for but also play a key role promoting retarding tumorigenesis context-dependent manner. CAFs have been involved modulation many immune system, recent studies revealed their roles evasion poor responses to cancer immunotherapy. In this review, we describe our current understanding tumorigenic significance, origin, heterogeneity CAFs, as well different subtypes distinct cell types. More importantly, highlight potential therapeutic strategies target unleash system against tumor.

Language: Английский

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Targeting MAPK Signaling in Cancer: Mechanisms of Drug Resistance and Sensitivity

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(3), P. 1102 - 1102

Published: Feb. 7, 2020

Mitogen-activated protein kinase (MAPK) pathways represent ubiquitous signal transduction that regulate all aspects of life and are frequently altered in disease. Here, we focus on the role MAPK modulating drug sensitivity resistance cancer. We briefly discuss new findings extracellular signaling-regulated (ERK) pathway, but mainly mechanisms how stress activated pathways, such as p38 Jun N-terminal kinases (JNK), impact response cancer cells to chemotherapies targeted therapies. In this context, also metabolic epigenetic aberrations therapeutic opportunities arising from these changes.

Language: Английский

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The role of collagen in cancer: from bench to bedside

Journal of Translational Medicine, Journal Year: 2019, Volume and Issue: 17(1)

Published: Sept. 14, 2019

Collagen is the major component of tumor microenvironment and participates in cancer fibrosis. biosynthesis can be regulated by cells through mutated genes, transcription factors, signaling pathways receptors; furthermore, collagen influence cell behavior integrins, discoidin domain receptors, tyrosine kinase some pathways. Exosomes microRNAs are closely associated with cancer. Hypoxia, which common collagen-rich conditions, intensifies progression, other substances extracellular matrix, such as fibronectin, hyaluronic acid, laminin, matrix metalloproteinases, interact to activity. Macrophages, lymphocytes, fibroblasts play a role immunity progression. Microscopic changes content within molecules ultimately contribute mutual feedback loop that influences prognosis, recurrence, resistance Nanoparticles, nanoplatforms, nanoenzymes exhibit expected gratifying properties. The pathophysiological functions diverse cancers illustrate dual roles provide promising therapeutic options readily translated from bench bedside. emerging understanding structural properties will guide development new strategies for anticancer therapy.

Language: Английский

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Circulating tumor cells: biology and clinical significance

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: Nov. 22, 2021

Abstract Circulating tumor cells (CTCs) are that have sloughed off the primary and extravasate into circulate in blood. Understanding of metastatic cascade CTCs has tremendous potential for identification targets against cancer metastasis. Detecting these very rare among massive blood is challenging. However, emerging technologies detection profoundly contributed to deepening investigation biology facilitated their clinical application. Current summarized herein, together with advantages disadvantages. The usually dependent on molecular markers, epithelial cell adhesion molecule being most widely used, although markers vary between different types cancer. Properties associated epithelial-to-mesenchymal transition stemness been identified CTCs, indicating increased capacity. Only a small proportion can survive eventually initiate metastases, suggesting an interaction modulation hostile microenvironment essential CTC Single-cell sequencing extensively investigated, enabled researchers reveal genome transcriptome CTCs. Herein, we also review applications especially monitoring response treatment evaluating prognosis. Hence, will continue contribute providing significant insights processes open new avenues useful applications.

Language: Английский

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