Cancer-associated fibroblasts: heterogeneity, tumorigenicity and therapeutic targets

Abstract Cancer, characterized by its immune evasion, active metabolism, and heightened proliferation, comprises both stroma and cells. Although the research has always focused on parenchymal cells, the non-parenchymal components must not be overlooked. Targeting cancer parenchymal cells has proven...

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Main Authors: Keke Lv, Tianlin He
Format: Article
Language:English
Published: Springer 2024-12-01
Series:Molecular Biomedicine
Subjects:
Online Access:https://doi.org/10.1186/s43556-024-00233-8
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author Keke Lv
Tianlin He
author_facet Keke Lv
Tianlin He
author_sort Keke Lv
collection DOAJ
description Abstract Cancer, characterized by its immune evasion, active metabolism, and heightened proliferation, comprises both stroma and cells. Although the research has always focused on parenchymal cells, the non-parenchymal components must not be overlooked. Targeting cancer parenchymal cells has proven to be a formidable challenge, yielding limited success on a broad scale. The tumor microenvironment(TME), a critical niche for cancer cell survival, presents a novel way for cancer treatment. Cancer-associated fibroblast (CAF), as a main component of TME, is a dynamically evolving, dual-functioning stromal cell. Furthermore, their biological activities span the entire spectrum of tumor development, metastasis, drug resistance, and prognosis. A thorough understanding of CAFs functions and therapeutic advances holds significant clinical implications. In this review, we underscore the heterogeneity of CAFs by elaborating on their origins, types and function. Most importantly, by elucidating the direct or indirect crosstalk between CAFs and immune cells, the extracellular matrix, and cancer cells, we emphasize the tumorigenicity of CAFs in cancer. Finally, we highlight the challenges encountered in the exploration of CAFs and list targeted therapies for CAF, which have implications for clinical treatment.
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spelling doaj-art-e51a95648b7948d687ede2e4746604102025-08-20T02:39:54ZengSpringerMolecular Biomedicine2662-86512024-12-015112210.1186/s43556-024-00233-8Cancer-associated fibroblasts: heterogeneity, tumorigenicity and therapeutic targetsKeke Lv0Tianlin He1Department of Hepatopanreatobiliary Surgery, Changhai HospitalDepartment of Hepatopanreatobiliary Surgery, Changhai HospitalAbstract Cancer, characterized by its immune evasion, active metabolism, and heightened proliferation, comprises both stroma and cells. Although the research has always focused on parenchymal cells, the non-parenchymal components must not be overlooked. Targeting cancer parenchymal cells has proven to be a formidable challenge, yielding limited success on a broad scale. The tumor microenvironment(TME), a critical niche for cancer cell survival, presents a novel way for cancer treatment. Cancer-associated fibroblast (CAF), as a main component of TME, is a dynamically evolving, dual-functioning stromal cell. Furthermore, their biological activities span the entire spectrum of tumor development, metastasis, drug resistance, and prognosis. A thorough understanding of CAFs functions and therapeutic advances holds significant clinical implications. In this review, we underscore the heterogeneity of CAFs by elaborating on their origins, types and function. Most importantly, by elucidating the direct or indirect crosstalk between CAFs and immune cells, the extracellular matrix, and cancer cells, we emphasize the tumorigenicity of CAFs in cancer. Finally, we highlight the challenges encountered in the exploration of CAFs and list targeted therapies for CAF, which have implications for clinical treatment.https://doi.org/10.1186/s43556-024-00233-8Cancer associated fibroblastsTumor microenvironmentExtracellular matrixImmune cellsMechanismsCancer cell
spellingShingle Keke Lv
Tianlin He
Cancer-associated fibroblasts: heterogeneity, tumorigenicity and therapeutic targets
Molecular Biomedicine
Cancer associated fibroblasts
Tumor microenvironment
Extracellular matrix
Immune cells
Mechanisms
Cancer cell
title Cancer-associated fibroblasts: heterogeneity, tumorigenicity and therapeutic targets
title_full Cancer-associated fibroblasts: heterogeneity, tumorigenicity and therapeutic targets
title_fullStr Cancer-associated fibroblasts: heterogeneity, tumorigenicity and therapeutic targets
title_full_unstemmed Cancer-associated fibroblasts: heterogeneity, tumorigenicity and therapeutic targets
title_short Cancer-associated fibroblasts: heterogeneity, tumorigenicity and therapeutic targets
title_sort cancer associated fibroblasts heterogeneity tumorigenicity and therapeutic targets
topic Cancer associated fibroblasts
Tumor microenvironment
Extracellular matrix
Immune cells
Mechanisms
Cancer cell
url https://doi.org/10.1186/s43556-024-00233-8
work_keys_str_mv AT kekelv cancerassociatedfibroblastsheterogeneitytumorigenicityandtherapeutictargets
AT tianlinhe cancerassociatedfibroblastsheterogeneitytumorigenicityandtherapeutictargets