Functional diversity of cancer‐associated fibroblasts in modulating drug resistance

Cancer Science, Год журнала: 2020, Номер 111(10), С. 3468 - 3477

Опубликована: Июль 23, 2020

Abstract The effectiveness of current chemotherapies for cancer is gradually progressing; however achieving a complete cure through chemotherapy still difficult and has been the main goal in treatment advanced cancer. Drug resistance an issue therapy, therefore increasing numbers investigations into drug have focused on characteristics cells themselves. interaction between tumor microenvironment (TME) also intimately involved development resistance. Cancer‐associated fibroblasts (CAFs) are predominant component TME affect progression by secreting soluble factors. This review summarizes most up‐to‐date knowledge CAFs cancer, with focus factors secreted from including proteins, cytokines, extracellular vesicles, metabolites. A perspective potential role anti‐CAF therapies overcoming CAF‐induced discussed.

Язык: Английский

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Paclitaxel-Based Chemotherapy Targeting Cancer Stem Cells from Mono- to Combination Therapy

Biomedicines, Год журнала: 2021, Номер 9(5), С. 500 - 500

Опубликована: Май 2, 2021

Paclitaxel (PTX) is a chemotherapeutical agent commonly used to treat several kinds of cancer. PTX known as microtubule-targeting with primary molecular mechanism that disrupts the dynamics microtubules and induces mitotic arrest cell death. Simultaneously, other mechanisms have been evaluated in many studies. Since anticancer activity was discovered, it has cancer patients become one most extensively drugs. Regrettably, resistance considered an extensive obstacle clinical applications major causes death correlated treatment failure. Therefore, combination drugs could lead efficient therapeutic strategies. Here, we summarize PTX, current studies focusing on review promising combinations.

Язык: Английский

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Deciphering the Role of Cancer Stem Cells: Drivers of Tumor Evolution, Therapeutic Resistance, and Precision Medicine Strategies

Cancers, Год журнала: 2025, Номер 17(3), С. 382 - 382

Опубликована: Янв. 24, 2025

Cancer stem cells (CSCs) play a central role in tumor progression, recurrence, and resistance to conventional therapies, making them critical focus oncology research. This review provides comprehensive analysis of CSC biology, emphasizing their self-renewal, differentiation, dynamic interactions with the microenvironment (TME). Key signaling pathways, including Wnt, Notch, Hedgehog, are discussed detail highlight potential as therapeutic targets. Current methodologies for isolating CSCs critically examined, addressing advantages limitations advancing precision medicine. Emerging technologies, such CRISPR/Cas9 single-cell sequencing, explored transformative unraveling heterogeneity informing strategies. The also underscores pivotal TME supporting survival, promoting metastasis, contributing resistance. Challenges arising from CSC-driven dormancy analyzed, along strategies mitigate these barriers, novel therapeutics targeted approaches. Ethical considerations integration artificial intelligence designing CSC-specific therapies essential elements future manuscript advocates multi-disciplinary approach that combines innovative advanced therapeutics, collaborative research address complexities CSCs. By bridging existing gaps knowledge fostering advancements personalized medicine, this aims guide development more effective cancer treatment strategies, ultimately improving patient outcomes.

Язык: Английский

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Significance of circulating tumor cells in lung cancer: a narrative review

Translational Lung Cancer Research, Год журнала: 2023, Номер 12(4), С. 877 - 894

Опубликована: Март 30, 2023

Background and Objective: In cancer patients, circulating tumor cells (CTCs) are employed as "Liquid Biopsy" for detection, prognosis assessment of the response to therapy.CTCs responsible dissemination but mechanisms involved in intravasation, survival circulation extravasation at secondary sites establish metastases not fully characterized.In lung CTCs present very high numbers small cell (SCLC) that is found disseminated most patients upon first presentation has a dismal prognosis.This review aims discussion recent work on metastatic SCLC novel insights into process derived from access panel unique CTC lines.Methods: PubMed Euro PMC were searched January 1 st , 2015 September 23 th 2022 using following key words: "SCLC", "NSCLC", "CTC" "Angiogenesis" supplemented by data our own work. KeyContent Findings: Experimental clinical indicate intravasation single, apoptotic or clustered occur via leaky neoangiogenetic vessels core crossing adjacent stroma after EMT.Furthermore, only EpCAM-positive have been prognostic impact.All established lines form spontaneously EpCAMpositive large chemoresistant spheroids (tumorospheres) may become trapped microvessels vivo suggested extravasate physical force.The rate-limiting step shedding likely presence irregular case SCLC, also formed vasculogenic mimicry.Therefore, lower microvessel densities (MVD) NSCLC can explain relative rarity versus SCLC.Conclusions: The detection lacks standardized techniques, difficult non-metastatic important biological need still be resolved, especially respect actual metastasis-inducing cells.Expression VEGF MVD indicators tumors ultimately, enumeration seems reflect vascular supply prognosis.

Язык: Английский

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DNA Methylation of Shelf, Shore and Open Sea CpG Positions Distinguish High Microsatellite Instability from Low or Stable Microsatellite Status Colon Cancer Stem Cells

Epigenomics, Год журнала: 2019, Номер 11(6), С. 587 - 604

Опубликована: Май 1, 2019

Aim: To investigate the genome-wide methylation of genetically characterized colorectal cancer stem cell (CR-CSC) lines. Materials & methods: Eight CR-CSC lines were isolated from primary (CRC) tissues, cultured and for aneuploidy, mutational status CRC-related genes microsatellite instability (MSI). Genome-wide DNA was assessed by MethylationEPIC microarray. Results: We describe a distinctive pattern that is maintained following in vivo passages immune-compromised mice. identified an epigenetic signature associated with MSI. noticed preponderance differentially methylated positions do not reside at CpG islands, but spread to shelf open sea regions. Conclusion: Given CRCs MSI-high have lower metastatic potential, identification MSI-related could provide new insights possible targets into CRC.

Язык: Английский

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Hedgehog-GLI signalling promotes chemoresistance through the regulation of ABC transporters in colorectal cancer cells

Scientific Reports, Год журнала: 2020, Номер 10(1)

Опубликована: Авг. 19, 2020

Colorectal cancer (CRC) is a leading cause of death. Chemoresistance pivotal feature cells to treatment failure and ATP-binding cassette (ABC) transporters are responsible for the efflux several molecules, including anticancer drugs. The Hedgehog-GLI (HH-GLI) pathway major signalling in CRC, however its role chemoresistance has not been fully elucidated. Here we show that HH-GLI favours resistance 5-fluorouracil Oxaliplatin CRC cells. We identified potential GLI1 binding sites promoter region six ABC transporters, namely ABCA2, ABCB1, ABCB4, ABCB7, ABCC2 ABCG1. Next, investigated using chromatin immunoprecipitation experiments demonstrate transcriptionally regulates transporters. chemoresistant express high levels inhibition disrupts up-regulation. Moreover, report human tumours ABCG1 transporter expression correlates with worse patients' prognosis. This study identifies new mechanism where features. Our results indicate Gli1 therefore should be considered as therapeutic option patients.

Язык: Английский

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Implication for Cancer Stem Cells in Solid Cancer Chemo-Resistance: Promising Therapeutic Strategies Based on the Use of HDAC Inhibitors

Journal of Clinical Medicine, Год журнала: 2019, Номер 8(7), С. 912 - 912

Опубликована: Июнь 26, 2019

Resistance to therapy in patients with solid cancers represents a daunting challenge that must be addressed. Indeed, current strategies are still not effective the majority of patients; which has resulted need for novel therapeutic approaches. Cancer stem cells (CSCs), subset tumor possess self-renewal and multilineage differentiation potential, known intrinsically resistant anticancer treatments. In this review, we analyzed implications CSCs drug resistance described multiple alterations morphogenetic pathways (i.e. Hippo, Wnt, JAK/STAT, TGF-, Notch, Hedgehog pathways) were suggested critical CSC plasticity. By interrogating The Genome Atlas (TCGA) datasets, first prevalence tumors associated outcomes. Then, by highlighting epigenetic relevance development maintenance, selected histone deacetylase inhibitors (HDACi) as potential agents interest target subpopulation based on pleiotropic effects exerted specifically altered pathways. detail, highlighted role HDACi and,specifically,in pointed out some mechanisms able overcome modulate stemness. Although, further clinical preclinical investigations should conducted disclose unclear several signaling different tumors. To date, lines evidence support testing combinatorial combination drugs commonly used practice improve efficacy cancer patients.

Язык: Английский

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L1CAM promotes ovarian cancer stemness and tumor initiation via FGFR1/SRC/STAT3 signaling

Journal of Experimental & Clinical Cancer Research, Год журнала: 2021, Номер 40(1)

Опубликована: Окт. 13, 2021

Cancer stem cells (CSC) have been implicated in tumor progression. In ovarian carcinoma (OC), CSC drive formation, dissemination and recurrence, as well drug resistance, thus contributing to the high death-to-incidence ratio of this disease. However, molecular basis such a pathogenic role (OCSC) has elucidated only limited extent. context, functional contribution L1 cell adhesion molecule (L1CAM) OC stemness remains elusive. The expression L1CAM was investigated patient-derived OCSC. genetic manipulation provided gain loss-of-function models that were then employed biological assays vivo tumorigenesis experiments assess OCSC-driven initiation. We applied antibody-mediated neutralization investigate druggability. Biochemical approaches combined with vitro study mechanisms underlying report is upregulated Functional studies showed promotes several stemness-related properties cells, including sphere initiation chemoresistance. These activities repressed by an L1CAM-neutralizing antibody, pointing druggable target. Mechanistically, interacted activated fibroblast growth factor receptor-1 (FGFR1), which turn induced SRC-mediated activation STAT3. inhibition STAT3 prevented L1CAM-dependent Our implicate tumorigenic function OCSC point L1CAM/FGFR1/SRC/STAT3 signaling pathway novel driver stemness. also provide evidence targeting can contribute eradication.

Язык: Английский

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Advancements in 3D In Vitro Models for Colorectal Cancer

Advanced Science, Год журнала: 2024, Номер 11(32)

Опубликована: Июль 4, 2024

Abstract The process of drug discovery and pre‐clinical testing is currently inefficient, expensive, time‐consuming. Most importantly, the success rate unsatisfactory, as only a small percentage tested drugs are made available to oncological patients. This largely due lack reliable models that accurately predict efficacy safety. Even animal often fail replicate human‐specific pathologies human body's complexity. These factors, along with ethical concerns regarding use, urge development suitable human‐relevant, translational in vitro models.

Язык: Английский

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Unveiling the future of cancer stem cell therapy: a narrative exploration of emerging innovations

Discover Oncology, Год журнала: 2025, Номер 16(1)

Опубликована: Март 22, 2025

Cancer stem cells (CSCs), are a critical subpopulation within tumours, and defined by their capacity for self-renewal, differentiation, tumour initiation. These unique traits contribute to progression, metastasis, resistance conventional treatments like chemotherapy radiotherapy, often resulting in cancer recurrence poor patient outcomes. As such, CSCs have become focal points developing advanced therapies. This review highlights progress CSC-targeted treatments, including chimeric antigen receptor T-cell (CAR-T) therapy, immunotherapy, molecular targeting, nanoparticle-based drug delivery systems. Plant-derived compounds gene-editing technologies, such as clustered regularly interspaced short palindromic repeats (CRISPR), explored potential enhance precision minimize side effects. Metabolic pathways integral CSC survival, mitochondrial dynamics, mitophagy (regulated dynamin-related protein 1 [DRP1] the PINK1/Parkin pathway), one-carbon metabolism, amino acid metabolism (involving enzymes glutaminase (GLS) glutamate dehydrogenase (GDH]), lipid hypoxia-induced metabolic reprogramming mediated hypoxia-inducible factors (HIF-1α HIF-2α), examined therapeutic targets. The adaptability of through autophagy, flexibility, epigenetic regulation metabolites α-ketoglutarate, succinate, fumarate is discussed. Additionally, extracellular vesicles nicotinamide adenine dinucleotide (NAD⁺) identified pivotal redox balance, DNA repair, modifications. Addressing challenges heterogeneity, immune evasion, treatment durability requires interdisciplinary collaboration. Advancing therapies essential overcoming preventing relapse, paving way transformative treatments. underscores importance leveraging innovative technologies fostering collaboration revolutionize treatment.

Язык: Английский

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