Cited by 1,007Cancer Cells and MetastasisMesenchymal stem cell researchTelomeres, Telomerase, and Senescence

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Cancer Stem Cells—Origins and Biomarkers: Perspectives for Targeted Personalized Therapies

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Walcher, Lia, Kistenmacher, Ann-Kathrin, Suo, Huizhen, Kitte, Reni, Dluczek, Sarah, Strauß, Alexander, Blaudszun, André-René, Yevsa, Tetyana, Fricke, Stephan, Kossatz-Boehlert, Uta·2020·Frontiers in Immunology

DOI 10.3389/fimmu.2020.01280PMC PMC7426526

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Abstract

The use of biomarkers in diagnosis, therapy and prognosis has gained increasing interest over the last decades. In particular, the analysis of biomarkers in cancer patients within the pre- and post-therapeutic period is required to identify several types of cells, which carry a risk for a disease progression and subsequent post-therapeutic relapse. Cancer stem cells (CSCs) are a subpopulation of tumor cells that can drive tumor initiation and can cause relapses. At the time point of tumor initiation, CSCs originate from either differentiated cells or adult tissue resident stem cells. Due to their importance, several biomarkers that characterize CSCs have been identified and correlated to diagnosis, therapy and prognosis. However, CSCs have been shown to display a high plasticity, which changes their phenotypic and functional appearance. Such changes are induced by chemo- and radiotherapeutics as well as senescent tumor cells, which cause alterations in the tumor microenvironment. Induction of senescence causes tumor shrinkage by modulating an anti-tumorigenic environment in which tumor cells undergo growth arrest and immune cells are attracted. Besides these positive effects after therapy, senescence can also have negative effects displayed post-therapeutically. These unfavorable effects can directly promote cancer stemness by increasing CSC plasticity phenotypes, by activating stemness pathways in non-CSCs, as well as by promoting senescence escape and subsequent activation of stemness pathways. At the end, all these effects can lead to tumor relapse and metastasis. This review provides an overview of the most frequently used CSC markers and their implementation as biomarkers by focussing on deadliest solid (lung, stomach, liver, breast and colorectal cancers) and hematological (acute myeloid leukemia, chronic myeloid leukemia) cancers. Furthermore, it gives examples on how the CSC markers might be influenced by therapeutics, such as chemo- and radiotherapy, and the tumor microenvironment. It points out, that it is crucial to identify and monitor residual CSCs, senescent tumor cells, and the pro-tumorigenic senescence-associated secretory phenotype in a therapy follow-up using specific biomarkers. As a future perspective, a targeted immune-mediated strategy using chimeric antigen receptor based approaches for the removal of remaining chemotherapy-resistant cells as well as CSCs in a personalized therapeutic approach are discussed.

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Authors: Walcher, L., Kistenmacher, A.-K., Suo, H., Kitte, R., Dluczek, S., Strauß, A., Blaudszun, A.-R., Yevsa, T., Fricke, S., & Kossatz-Boehlert, U.
Affiliations: Fraunhofer Institute for Cell Therapy and Immunology (DE)
Medizinische Hochschule Hannover (DE)
Corresponding author: Yevsa, Tetyana
Kossatz-Boehlert, Uta
ORCID: Walcher, Lia
Strauß, Alexander
Blaudszun, André-René
Yevsa, Tetyana
Fricke, Stephan
Kossatz-Boehlert, Uta
Venue: Frontiers in Immunology
Publisher: Frontiers Media SA
Published: 2020-08-07
Volume: 11
Pages: 1280-1280
ISSN: 1664-3224 (ISSN-L)
DOI: 10.3389/fimmu.2020.01280
PMC: PMC7426526
OpenAlex: W3047693299
Cited by: 1,007
References: 603
Citations by year: 2026: 75 · 2025: 177 · 2024: 284 · 2023: 244 · 2022: 170 · 2021: 52 · 2020: 5
FWCI: 12.67
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
Locations: Frontiers in Immunology (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Publikationsdatenbank der Fraunhofer-Gesellschaft (Fraunhofer-Gesellschaft) (submittedVersion, other-oa)
Fraunhofer-Publica (Fraunhofer-Gesellschaft) (submittedVersion)
Funders: Deutsche Forschungsgemeinschaft (YE 151/2-1, AOBJ: 618426)
Fraunhofer-Gesellschaft
Fritz Thyssen Stiftung (REF.10.16.1.031MN)
Sächsische Aufbaubank
Topics: Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
Keywords: cancer stem cells, tumor recurrence, senescence-associated secretory phenotype, senescence escape, tumor microenvironment, chemoresistance, radiotherapy, chimeric antigen receptor T cells, precision oncology, acute myeloid leukemia, chronic myeloid leukemia, solid tumors, hematologic cancer
MeSH terms: Animals, Combined Modality Therapy, Disease Susceptibility, Humans, Neoplasms, Organ Specificity, Prognosis, Biomarkers, Tumor, Neoplastic Stem Cells, Biomarkers, Immunotherapy, Adoptive, Cellular Senescence, Disease Progression, Drug Resistance, Neoplasm, Disease Management, Molecular Diagnostic Techniques, Precision Medicine, Molecular Targeted Therapy

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Cancer Stem Cells—Origins and Biomarkers: Perspectives for Targeted Personalized Therapies

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