☆ 4.6 Review

Cancer Stem Cells and Glioblastoma: Time for Innovative Biomarkers of Radio-Resistance?

BIOLOGY-BASEL (2023)

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Review Cell Biology

Roles of STAT3 in the pathogenesis and treatment of glioblastoma

Weijia Fu et al.

Summary: Glioblastoma (GBM) is a highly malignant brain tumor. The IL6/JAK/STAT3 signaling pathway plays a crucial role in the development and progression of GBM. Abnormal activation of STAT3 in GBM leads to immunosuppression and blocking this pathway can effectively inhibit tumor growth and metastasis. Inhibiting STAT3 may provide a new therapeutic approach for GBM, and combining STAT3 targeted therapy with conventional treatments could improve the current status of GBM treatment.

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY (2023)

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Review Biology

Tumor Microenvironment and Glioblastoma Cell Interplay as Promoters of Therapeutic Resistance

Edoardo Agosti et al.

Summary: Despite advancements in molecular discoveries and surgical technologies, the prognosis for glioblastoma (GBM) remains poor. Tumor recurrence, particularly of GBM, could be attributed to the persistence of a subset of cancer cells with stem cell characteristics. The tumor microenvironment (TME) and its interaction with GBM stem cells have been identified as crucial factors in recurrence, making them potential targets for new therapeutic approaches.

BIOLOGY-BASEL (2023)

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Review Oncology

The impact of survivorship bias in glioblastoma research

Francesco Pasqualetti et al.

Summary: Despite advances in CNS malignancies therapy, GB treatment remains challenging due to resistance and high recurrence rates. Most predictive GB biomarkers are developed using surgical samples, but selection criteria vary among neurosurgeons, making the patients not representative. Survivorship bias affects biomarkers for patient selection, therapy, and outcome analyses.

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HIF1α/HIF2α induces glioma cell dedifferentiation into cancer stem cells through Sox2 under hypoxic conditions

Pan Wang et al.

Summary: The study demonstrated that in a hypoxic microenvironment, the HIF1 alpha/HIF2 alpha-Sox2 network induced the formation of glioma stem cells through the dedifferentiation of differentiated glioma cells, thus promoting glioma cell chemoresistance. Both HIF1 alpha and HIF2 alpha, as genes upstream of Sox2, regulate the malignant progression of glioma through dedifferentiation. The knockout of HIF1 alpha, HIF2 alpha, and Sox2 in glioma cells under hypoxic conditions led to decreased CD133 and CD15 expression and inhibited sphere formation.

JOURNAL OF CANCER (2022)

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The ALDH Family Contributes to Immunocyte Infiltration, Proliferation and Epithelial-Mesenchymal Transformation in Glioma

Zeyu Wang et al.

Summary: In this study, the role of the aldehyde dehydrogenase family in gliomas was explored through bulk RNA-seq analysis and single-cell RNA-Seq analysis. The results showed that high-scoring samples based on the aldehyde dehydrogenases family were associated with worse survival outcomes. Pathway enrichment scores were calculated to validate the biofunction prediction results, indicating that the aldehyde dehydrogenases family influenced glioma progression by modulating tumor cell proliferation, migration, and immune landscape. ALDH3B1 and ALDH16A1, two main contributors to the scoring system, were found to affect glioblastoma cell proliferation and migration through cell-cycle arrest and the epithelial-mesenchymal transition.

FRONTIERS IN IMMUNOLOGY (2022)

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Role of CD133/NRF2 Axis in the Development of Colon Cancer Stem Cell-Like Properties

Jimin Park et al.

Summary: This study investigated the potential relationship between the CSC marker CD133 and the master transcription factor NRF2 in colon cancer. The results indicate that the CD133/NRF2 axis plays a critical role in the development of CSC-like properties in colon cancer cells, with activation of the PI3K/AKT signaling pathway involved in CD133-mediated NRF2 activation.

FRONTIERS IN ONCOLOGY (2022)

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Tumor-associated macrophage derived IL-6 enriches cancer stem cell population and promotes breast tumor progression via Stat-3 pathway

N. N. Radharani et al.

Summary: Tumor-associated macrophages (TAMs) promote tumor progression by interacting with breast cancer cells, expressing various proteins, including cytokines that enrich cancer stem cells (CSCs). TAMs produce high levels of Interleukin-6 (IL-6) through p38-MAPK pathway upon interaction with breast cancer cells. TAM-derived IL-6 activates Signal transducer and activator of transcription 3 (STAT-3) pathway, promotes CSC enrichment and influences tumor growth in breast cancer.

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IDH mutation and cancer stem cell

Yang Zhang et al.

Summary: Cancer stem cells (CSCs) have a close relationship with oncogenesis, disease progression, therapeutic resistance, and overall outcome. Mutations in isocitrate dehydrogenase (IDH) are closely related to the establishment and maintenance of CSCs, leading to distinctive molecular signatures. IDH mutation and IDH-related pathways could be valuable molecular targets to improve the disease outcome.

ESSAYS IN BIOCHEMISTRY (2022)

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Extracellular Vesicles Secreted by Glioma Stem Cells Are Involved in Radiation Resistance and Glioma Progression

Chenkai Ma et al.

Summary: This study found that extracellular vesicles (EVs) secreted by glioma stem cells (GSC-EVs) have the potential to induce radiation resistance and promote glioma progression. GSC-EVs activate the PTEN/Akt pathway in recipient cells through specific miRNAs, leading to phenotypic changes and increased cell migration and colony formation.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

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Epidemiology of Glioblastoma Multiforme-Literature Review

Szymon Grochans et al.

Summary: Glioblastoma multiforme (GBM) is a highly aggressive malignancy with a median overall survival of approximately 15 months. This review analyzes the pathogenesis and epidemiological data of GBM, including age, gender, and tumor location. The data suggest that GBM is a higher-grade primary brain tumor and is significantly more common in men. Despite advancements in medicine, the risk of being diagnosed with glioma increases with age and median survival remains low. Additionally, the influence of stimulants, certain medications (such as NSAIDs), cell phone use, and exposure to heavy metals on GBM is difficult to determine clearly.

CANCERS (2022)

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Current Understanding of Hypoxia in Glioblastoma Multiforme and Its Response to Immunotherapy

Jang Hyun Park et al.

Summary: Glioblastoma multiforme (GBM) is an aggressive tumor in the central nervous system, and its survival is affected by hypoxia, which promotes drug resistance and inhibits immune responses. Traditionally, hypoxia studies have focused on blood vessels and tumor cells, excluding the immune system. However, recent evidence suggests the important role of immunosurveillance in tumor hypoxia. This review discusses the clinical, pathological, and immunological perspectives of hypoxia in GBM.

CANCERS (2022)

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Emerging Roles of Aldehyde Dehydrogenase Isoforms in Anti-cancer Therapy Resistance

Michele Zanoni et al.

Summary: Aldehyde dehydrogenases (ALDHs) are detoxifying enzymes often upregulated in cancer cells and associated with therapeutic resistance. ALDHs have various functions in cancer stem cells and immune cells, playing a crucial role in cancer treatment.

FRONTIERS IN MEDICINE (2022)

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Cytokine-mediated crosstalk between cancer stem cells and their inflammatory niche from the colorectal precancerous adenoma stage to the cancerous stage: Mechanisms and clinical implications

Guanglin Cui et al.

Summary: The development of colorectal cancer is closely related to cytokines, which play an important role in the regulation of pCSC/CSC properties and features.

FRONTIERS IN IMMUNOLOGY (2022)

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Circular EZH2-encoded EZH2-92aa mediates immune evasion in glioblastoma via inhibition of surface NKG2D ligands

Jian Zhong et al.

Summary: This study revealed that the overexpression of EZH2-92aa in Glioblastoma leads to immune evasion of the tumor cells from NK cells. EZH2-92aa directly binds and represses the transcription of MICA/B, and indirectly represses ULBP transcription by stabilizing EZH2. Knockdown of EZH2-92aa enhances NK cell-mediated eradication of GSCs and synergizes with anti-PD1 therapy.

NATURE COMMUNICATIONS (2022)

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The emerging role of exosomes in radiotherapy

Zhenyi Yang et al.

Summary: Radiotherapy is commonly used in cancer treatment, but radioresistance and radiation-induced bystander effects remain challenging. Exosomes play a significant role in radiotherapy by mediating intercellular signaling pathways and participating in the mechanisms of radioresistance and radiation-induced bystander effects.

CELL COMMUNICATION AND SIGNALING (2022)

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New perspectives in liquid biopsy for glioma patients

Francesco Pasqualetti et al.

Summary: Although studies on the use of liquid biopsy are still at an early stage, the potential clinical applications of liquid biopsy in the study of primary brain cancer are many and have the potential to revolutionize the approach to neuro-oncology, and importantly, they offer the possibility of gathering information on the disease at any time during its history.

CURRENT OPINION IN ONCOLOGY (2022)

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Cancer Stem Cells and the Tumor Microenvironment: Targeting the Critical Crosstalk through Nanocarrier Systems

Aadya Nayak et al.

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EZH2 is a potential prognostic predictor of glioma

Yi-nan Chen et al.

Summary: The study found that the expression of EZH2 in glioma is significantly correlated with clinicopathologic characteristics and overall survival rate, suggesting its potential as a prognostic molecular marker. Additionally, the research identified associations between EZH2 and signaling pathways related to the cell cycle, DNA replication, and immune checkpoints.

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EANO guidelines on the diagnosis and treatment of diffuse gliomas of adulthood

Michael Weller et al.

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NATURE REVIEWS CLINICAL ONCOLOGY (2021)

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Hypoxia-Induced Cancer Cell Responses Driving Radioresistance of Hypoxic Tumors: Approaches to Targeting and Radiosensitizing

Alexander E. Kabakov et al.

Summary: Certain cancer cells become more resistant to radiation under hypoxic conditions, decreasing the efficacy of radiotherapy for hypoxic tumors. Understanding the mechanisms by which cancer cells adapt to hypoxia can help improve the sensitivity of hypoxic tumors to radiotherapy.

CANCERS (2021)

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SOX2 promotes chemoresistance, cancer stem cells properties, and epithelial-mesenchymal transition by β-catenin and Beclin1/autophagy signaling in colorectal cancer

Yin Zhu et al.

Summary: The study elucidated the mechanisms by which SOX2 regulates ABCC2 in colorectal cancer, along with beta-catenin, Beclin1, and autophagy signaling, affecting chemoresistance, stemness, and EMT. Clinical analyses revealed a positive correlation between high ABCC2 and Beclin1 expression with SOX2, associated with poor prognosis in CRC patients. Xenograft models confirmed that inhibition of SOX2 expression and autophagy restrained tumor growth and chemoresistance in vivo.

CELL DEATH & DISEASE (2021)

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Metastasis-Initiating Cells and Ecosystems

Joan Massague et al.

Summary: Metastasis-initiating cells (MIC) are cancer cells with stem-like and immune-evasive properties that adopt regenerative progenitor phenotypes, enabling them to survive the stresses of metastasis and evade immune surveillance. Understanding the molecular mechanisms of MIC phenotypes and host tissue ecosystems is crucial for developing improved cancer therapeutics.

CANCER DISCOVERY (2021)

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Role of glioblastoma stem cells in cancer therapeutic resistance: a perspective on antineoplastic agents from natural sources and chemical derivatives

Ana Laura V. Alves et al.

Summary: Glioblastoma (GBM) is the highest-grade form of glioma, characterized by rapid cellular growth and high invasiveness. Understanding cancer stem cells (CSCs) has provided new insights into GBM resistance and management. With knowledge of GSCs and therapies based on antineoplastic agents, a promising future in GBM treatment may be on the horizon.

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Terence Kin-Wah Lee et al.

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NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY (2021)

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Glioma Stem-Like Cells and Metabolism: Potential for Novel Therapeutic Strategies

Abigail Harland et al.

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Hiroyuki Tsuchiya et al.

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CD44-associated radioresistance of glioblastoma in irradiated brain areas with optimal tumor coverage

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CANCER MEDICINE (2020)

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Glioblastoma Stem Cell-Derived Exosomes Enhance Stemness and Tumorigenicity of Glioma Cells by Transferring Notch1 Protein

Zhen Sun et al.

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Julia Lopez de Andres et al.

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Tim-3 Expression and MGMT Methylation Status Association With Survival in Glioblastoma

Ji Zhang et al.

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EZH2-Inhibited MicroRNA-454-3p Promotes M2 Macrophage Polarization in Glioma

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Seda Tuncay Cagatay et al.

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Putative cancer stem cells may be the key target to inhibit cancer cell repopulation between the intervals of chemoradiation in murine mesothelioma

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CD44: More than a mere stem cell marker

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Immunohistochemical expression of stem cell markers CD44 and nestin in glioblastomas: Evaluation of their prognostic significance

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The Vascular Notch Ligands Delta-Like Ligand 4 (DLL4) and Jagged1 (JAG1) Have Opposing Correlations with Microvascularization but a Uniform Prognostic Effect in Primary Glioblastoma: A Preliminary Study

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WORLD NEUROSURGERY (2016)

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Ranjeeta Thapa et al.

STEM CELLS INTERNATIONAL (2016)

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EZH2 Protects Glioma Stem Cells from Radiation-Induced Cell Death in a MELK/FOXMI-Dependent Manner

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Epidermal growth factor receptor variant III renders glioma cancer cells less differentiated by JAGGED1

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Article Biochemistry & Molecular Biology

Oct-3/4 promotes migration and invasion of glioblastoma cells

Kana Kobayashi et al.

JOURNAL OF CELLULAR BIOCHEMISTRY (2012)

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Article Multidisciplinary Sciences

A restricted cell population propagates glioblastoma growth after chemotherapy

Jian Chen et al.

NATURE (2012)

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Article Medicine, General & Internal

Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing

Marco Gerlinger et al.

NEW ENGLAND JOURNAL OF MEDICINE (2012)

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Article Oncology

Chk1 knockdown confers radiosensitization in prostate cancer stem cells

Xiaobin Wang et al.

ONCOLOGY REPORTS (2012)

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Article Cell & Tissue Engineering

Monoclonal Antibodies Against Lgr5 Identify Human Colorectal Cancer Stem Cells

Kristel Kemper et al.

STEM CELLS (2012)

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Editorial Material Cell Biology

Notch Signaling

Raphael Kopan

COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY (2012)

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Article Oncology

Breast cancer stem-like cells show dominant homologous recombination due to a larger S-G2 fraction

Osama Al-Assar et al.

CANCER BIOLOGY & THERAPY (2011)

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Article Urology & Nephrology

Exosomes as Biomarker Treasure Chests for Prostate Cancer

Diederick Duijvesz et al.

EUROPEAN UROLOGY (2011)

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Article Multidisciplinary Sciences

The Phenotypic Radiation Resistance of CD44+/CD24-or low Breast Cancer Cells Is Mediated through the Enhanced Activation of ATM Signaling

Hong Yin et al.

PLOS ONE (2011)

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Review Oncology

Quiescent, Slow-Cycling StemCell Populations in Cancer: A Review of the Evidence and Discussion of Significance

Nathan Moore et al.

JOURNAL OF ONCOLOGY (2011)

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Review Oncology

GENOMIC INSTABILITY IN CANCER Strategies to improve radiotherapy with targeted drugs

Adrian C. Begg et al.

NATURE REVIEWS CANCER (2011)

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Article Biochemistry & Molecular Biology

Knock down of HIF-1α in glioma cells reduces migration in vitro and invasion in vivo and impairs their ability to form tumor spheres

Olga Mendez et al.

MOLECULAR CANCER (2010)

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Article Oncology

Survival and self-renewing capacity of breast cancer initiating cells during fractionated radiation treatment

Chann Lagadec et al.

BREAST CANCER RESEARCH (2010)

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Article Multidisciplinary Sciences

Association of reactive oxygen species levels and radioresistance in cancer stem cells

Maximilian Diehn et al.

NATURE (2009)

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Article Oncology

Therapeutic Implications of the Cancer Stem Cell Hypothesis

Maximilian Diehn et al.

SEMINARS IN RADIATION ONCOLOGY (2009)

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Article Cell & Tissue Engineering

STAT3 Is Required for Proliferation and Maintenance of Multipotency in Glioblastoma Stem Cells

Maureen M. Sherry et al.

STEM CELLS (2009)

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Article Genetics & Heredity

Comparison of nonhomologous end joining and homologous recombination in human cells

Zhiyong Mao et al.

DNA REPAIR (2008)

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Article Oncology

Nestin and CD133: valuable stem cell-specific markers for determining clinical outcome of glioma patients

Mingyu Zhang et al.

JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH (2008)

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Article Biochemistry & Molecular Biology

Identification and expansion of the tumorigenic lung cancer stem cell population

A. Eramo et al.

CELL DEATH AND DIFFERENTIATION (2008)

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Article Oncology

Nestin, PDGFRβ, CXCL12 and VEGF in glioma patients -: Different profiles of (pro-angiogenic) molecule expression are related with tumor grade and may provide prognostic information

Ernanuela Maderna et al.

CANCER BIOLOGY & THERAPY (2007)

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Article Multidisciplinary Sciences

WNT/β-catenin mediates radiation resistance of mouse mammary progenitor cells

Wendy A. Woodward et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2007)

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Article Oncology

A perivascular niche for brain tumor stem cells

Christopher Calabrese et al.

CANCER CELL (2007)

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Article Cell Biology

Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells

Hadi Valadi et al.

NATURE CELL BIOLOGY (2007)

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Article Oncology

The response of CD24-/low/CD44+ breast cancer-initiating cells to radiation

Tiffany M. Phillips et al.

JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE (2006)

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Article Multidisciplinary Sciences

Glioma stem cells promote radioresistance by preferential activation of the DNA damage response

Shideng Bao et al.

NATURE (2006)

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Review Oncology

Hypoxia and the hypoxia-inducible-factor pathway in glioma growth and angiogenesis

B Kaur et al.

NEURO-ONCOLOGY (2005)

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Article Medicine, General & Internal

Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma

R Stupp et al.

NEW ENGLAND JOURNAL OF MEDICINE (2005)

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Article Multidisciplinary Sciences

Identification of human brain tumour initiating cells

SK Singh et al.

NATURE (2004)

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Article Multidisciplinary Sciences

Prospective identification of tumorigenic breast cancer cells

M Al-Hajj et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2003)

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