The molecular features of lung cancer stem cells (LCSCs) in dedifferentiation process-driven epigenetic alterations DOI Creative Commons
Valentina Masciale, Federico Banchelli, Giulia Grisendi

et al.

Journal of Biological Chemistry, Journal Year: 2024, Volume and Issue: unknown, P. 107994 - 107994

Published: Nov. 1, 2024

Cancer stem cells (CSCs) may be dedifferentiated somatic following oncogenic processes, representing a subpopulation of able to promote tumor growth with their capacities for proliferation and self-renewal, inducing lineage heterogeneity, which main cause resistance therapies. It has been shown that the "less differentiated process" have an impact on plasticity, particularly when non-CSCs dedifferentiate become CSC-like. Bidirectional interconversion between CSCs reported in other solid tumors, where inflammatory stroma promotes cell reprogramming by enhancing Wnt signaling through NF-κB activation association intracellular signaling, induce cells' pluripotency, transformation can considered another important aspect acquisition "new" development programs features. During reprogramming, mutations represent initial step towards dedifferentiation, tumour switch from partially or terminally stage less is mainly manifested re-entry into cycle, cell-like phenotype expression markers. This phenomenon typically shows up as change form, function, pattern gene protein expression, more specifically, CSCs. review would highlight epigenetic alterations, major pathways driver cancer cells, tumors lung cancer, could involved, acting key elements differentiation/dedifferentiation process. molecular mechanisms need tailored

Language: Английский

Patient-derived organoids in human cancer: a platform for fundamental research and precision medicine DOI Creative Commons
Shanqiang Qu, Rongyang Xu,

Guozhong Yi

et al.

Molecular Biomedicine, Journal Year: 2024, Volume and Issue: 5(1)

Published: Feb. 12, 2024

Abstract Cancer is associated with a high degree of heterogeneity, encompassing both inter- and intra-tumor along considerable variability in clinical response to common treatments across patients. Conventional models for tumor research, such as vitro cell cultures vivo animal models, demonstrate significant limitations that fall short satisfying the research requisites. Patient-derived organoids, which recapitulate structures, specific functions, molecular characteristics, genomics alterations expression profiles primary tumors. They have been efficaciously implemented illness portrayal, mechanism exploration, high-throughput drug screening assessment, discovery innovative therapeutic targets potential compounds, customized treatment regimen cancer In contrast conventional organoids offer an intuitive, dependable, efficient model by conserving phenotypic, genetic diversity, mutational attributes originating tumor. Nevertheless, organoid technology also confronts bottlenecks challenges, how comprehensively reflect microenvironment, angiogenesis, reduce costs, establish standardized construction processes while retaining reliability. This review extensively examines use techniques fundamental precision medicine. It emphasizes importance patient-derived biobanks development, screening, safety evaluation, personalized Additionally, it evaluates application experimental better understand mechanisms The intent this explicate significance present new avenues future research.

Language: Английский

Citations

18
Signaling pathways in the regulation of cancer stem cells and associated targeted therapy DOI Creative Commons
Manni Wang,

Wu Min

MedComm, Journal Year: 2022, Volume and Issue: 3(4)

Published: Oct. 5, 2022

Cancer stem cells (CSCs) are defined as a subpopulation of malignant tumor with selective capacities for initiation, self-renewal, metastasis, and unlimited growth into bulks, which believed major cause progressive phenotypes, including recurrence, treatment failure. A number signaling pathways involved in the maintenance cell properties survival CSCs, well-established intrinsic pathways, such Notch, Wnt, Hedgehog signaling, extrinsic vascular microenvironment tumor-associated immune cells. There is also intricate crosstalk between these signal cascades other oncogenic pathways. Thus, targeting pathway molecules that regulate CSCs provides new option therapy-resistant or -refractory tumors. These treatments include small molecule inhibitors, monoclonal antibodies target key well CSC-directed immunotherapies harness systems to CSCs. This review aims provide an overview regulating networks their interactions CSC development. We address update on development therapeutics, special focus those application approval under clinical evaluation.

Language: Английский

Citations

45
Unraveling the underlying mechanisms of cancer stem cells in therapeutic resistance for optimizing treatment strategies DOI Creative Commons

Yunhan Tan,

Siyuan Qin, Zhe Zhang

et al.

MedComm – Oncology, Journal Year: 2025, Volume and Issue: 4(1)

Published: Jan. 10, 2025

Abstract The success of cancer therapy has been significantly hampered by various mechanisms therapeutic resistance. Chief among these is the presence clonal heterogeneity within an individual tumor mass. introduction concept stem cells (CSCs)—a rare and immature subpopulation with tumorigenic potential that contributes to intratumoral heterogeneity—has deepened our understanding drug Given characteristics CSCs, such as increased drug‐efflux activity, enhanced DNA‐repair capacity, high metabolic plasticity, adaptability oxidative stress, and/or upregulated detoxifying aldehyde dehydrogenase (ALDH) enzymes, CSCs have recognized a theoretical reservoir for resistant diseases. Implicit in this recognition possibility CSC‐targeted strategies might offer breakthrough overcoming resistance patients. Herein, we summarize generation current underlying CSC‐mediated This extended knowledge progressively translated into novel anticancer enriched available options combination treatments, all which are anticipated improve clinical outcomes patients experiencing CSC‐related relapse.

Language: Английский

Citations

1
Cancer stem cells and tumor-associated macrophages as mates in tumor progression: mechanisms of crosstalk and advanced bioinformatic tools to dissect their phenotypes and interaction DOI Creative Commons
Francesco Verona, Sebastiano Di Bella,

Roberto Schirano

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 6, 2025

Cancer stem cells (CSCs) are a small subset within the tumor mass significantly contributing to cancer progression through dysregulation of various oncogenic pathways, driving growth, chemoresistance and metastasis formation. The aggressive behavior CSCs is guided by several intracellular signaling pathways such as WNT, NF-kappa-B, NOTCH, Hedgehog, JAK-STAT, PI3K/AKT1/MTOR, TGF/SMAD, PPAR MAPK kinases, well extracellular vesicles exosomes, molecules cytokines, chemokines, pro-angiogenetic growth factors, which finely regulate CSC phenotype. In this scenario, microenvironment (TME) key player in establishment permissive niche, where engage intricate communications with diverse immune cells. "oncogenic" mainly represented B T lymphocytes, NK cells, dendritic Among macrophages exhibit more plastic adaptable phenotype due their different subpopulations, characterized both immunosuppressive inflammatory phenotypes. Specifically, tumor-associated (TAMs) create an milieu production plethora paracrine factors (IL-6, IL-12, TNF-alpha, TGF-beta, CCL1, CCL18) promoting acquisition stem-like, invasive metastatic TAMs have demonstrated ability communicate via direct ligand/receptor (such CD90/CD11b, LSECtin/BTN3A3, EPHA4/Ephrin) interaction. On other hand, exhibited capacity influence creating favorable for progression. Interestingly, bidirectional TME leads epigenetic reprogramming sustains malignant transformation. Nowadays, integration biological computational data obtained cutting-edge technologies (single-cell RNA sequencing, spatial transcriptomics, trajectory analysis) has improved comprehension biunivocal multicellular dialogue, providing comprehensive view heterogeneity dynamics CSCs, uncovering alternative mechanisms evasion therapeutic resistance. Moreover, combination biology will lead development innovative target therapies dampening CSC-TME Here, we aim elucidate most recent insights on complex interactions specifically TAMs, tracing exhaustive scenario from primary

Language: Английский

Citations

1
Regulatory network and targeted interventions for CCDC family in tumor pathogenesis DOI
Zhen Liu, Weiwei Yan,

Shaohua Liu

et al.

Cancer Letters, Journal Year: 2023, Volume and Issue: 565, P. 216225 - 216225

Published: May 12, 2023

Language: Английский

Citations

20
Targeting autophagy and lipid metabolism in cancer stem cells DOI

Bandana Chakravarti,

Jawed A. Siddiqui, Rohit A. Sinha

et al.

Biochemical Pharmacology, Journal Year: 2023, Volume and Issue: 212, P. 115550 - 115550

Published: April 13, 2023

Language: Английский

Citations

17
Intricate relationship between cancer stemness, metastasis, and drug resistance DOI Creative Commons
Tikam Chand Dakal, Ravi Bhushan, Caiming Xu

et al.

MedComm, Journal Year: 2024, Volume and Issue: 5(10)

Published: Sept. 21, 2024

Cancer stem cells (CSCs) are widely acknowledged as the drivers of tumor initiation, epithelial-mesenchymal transition (EMT) progression, and metastasis. Originating from both hematologic solid malignancies, CSCs exhibit quiescence, pluripotency, self-renewal akin to normal cells, thus orchestrating heterogeneity growth. Through a dynamic interplay with microenvironment (TME) intricate signaling cascades, undergo transitions differentiated cancer culminating in therapy resistance disease recurrence. This review undertakes an in-depth analysis multifaceted mechanisms underlying stemness CSC-mediated therapy. Intrinsic factors encompassing TME, hypoxic conditions, oxidative stress, alongside extrinsic processes such drug efflux mechanisms, collectively contribute therapeutic resistance. An exploration into key pathways, including JAK/STAT, WNT, NOTCH, HEDGEHOG, sheds light on their pivotal roles sustaining phenotypes. Insights gleaned preclinical clinical studies hold promise refining discovery efforts optimizing interventions, especially chimeric antigen receptor (CAR)-T cell therapy, cytokine-induced killer (CIK) natural (NK) cell-mediated CSC-targeting others. Ultimately use sorting single sequencing approaches for elucidating fundamental characteristics inherent will enhance our comprehension CSC intratumor heterogeneity, which ultimately would inform about tailored personalized interventions.

Language: Английский

Citations

8
Cancer stem cells: a target for overcoming therapeutic resistance and relapse DOI Creative Commons
Shuo Zhang, Rui Yang,

Yujie Ouyang

et al.

Cancer Biology and Medicine, Journal Year: 2024, Volume and Issue: 20(12), P. 985 - 1020

Published: Jan. 2, 2024

Cancer stem cells (CSCs) are a small subset of in cancers that thought to initiate tumorous transformation and promote metastasis, recurrence, resistance treatment. Growing evidence has revealed the existence CSCs various types suggested differentiate into diverse lineage contribute tumor progression. We may be able overcome limitations cancer treatment with comprehensive understanding biological features mechanisms underlying therapeutic CSCs. This review provides an overview properties, biomarkers, shown by Recent findings on metabolic features, especially fatty acid metabolism ferroptosis CSCs, highlighted, along promising targeting strategies. Targeting is potential plan conquer prevent relapse

Language: Английский

Citations

6
Comprehensive review of drug resistance in mammalian cancer stem cells: implications for cancer therapy DOI Creative Commons

Bemrew Admassu Mengistu,

Tirunesh Tsegaw,

Yitayew Demessie

et al.

Cancer Cell International, Journal Year: 2024, Volume and Issue: 24(1)

Published: Dec. 18, 2024

Cancer remains a significant global challenge, and despite the numerous strategies developed to advance cancer therapy, an effective cure for metastatic elusive. A major hurdle in treatment success is ability of cells, particularly stem cells (CSCs), resist therapy. These CSCs possess unique abilities, including self-renewal, differentiation, repair, which drive tumor progression chemotherapy resistance. The resilience linked certain signaling pathways. Tumors with pathway-dependent often develop genetic resistance, whereas those pathway-independent undergo epigenetic changes that affect gene regulation. can evade cytotoxic drugs, radiation, apoptosis by increasing drug efflux transporter activity activating survival mechanisms. Future research should prioritize identification new biomarkers molecules better understand use cutting-edge approaches, such as bioinformatics, genomics, proteomics, nanotechnology, offers potential solutions this challenge. Key include developing targeted therapies, employing nanocarriers precise delivery, focusing on CSC-targeted pathways Wnt, Notch, Hedgehog Additionally, investigating multitarget inhibitors, immunotherapy, nanodrug delivery systems critical overcoming resistance cells.

Language: Английский

Citations

6
Suppression of NANOG Expression Reduces Drug Resistance of Cancer Stem Cells in Glioblastoma DOI Open Access

Jonhoi Smith,

Melvin Field, Kimio Sugaya

et al.

Genes, Journal Year: 2023, Volume and Issue: 14(6), P. 1276 - 1276

Published: June 16, 2023

Glioblastoma (GBM) is an aggressive and incurable primary brain tumor that harbors therapy-resistant cancer stem cells (CSCs). Due to the limited effectiveness of conventional chemotherapies radiation treatments against CSCs, there a critical need for development innovative therapeutic approaches. Our previous research revealed significant expression embryonic stemness genes, NANOG OCT4, in suggesting their role enhancing cancer-specific drug resistance. In our current study, we employed RNA interference (RNAi) suppress these genes observed increased susceptibility CSCs anticancer drug, temozolomide (TMZ). Suppression induced cell cycle arrest specifically G0 phase, it concomitantly decreased PDK1. Since PDK1 activates PI3K/AKT pathway promote proliferation survival, findings suggest contributes chemotherapy resistance through activation. Therefore, combination TMZ treatment with RNAi targeting holds promise as strategy GBM.

Language: Английский

Citations

16