Therapy-induced secretion of spliceosomal components mediates pro-survival crosstalk between ovarian cancer cells DOI Creative Commons
Victoria О. Shender, Ksenia S. Anufrieva, Polina V. Shnaider

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: June 19, 2024

Abstract Ovarian cancer often develops resistance to conventional therapies, hampering their effectiveness. Here, using ex vivo paired ovarian ascites obtained before and after chemotherapy in vitro therapy-induced secretomes, we show that molecules secreted by cells upon therapy promote cisplatin enhance DNA damage repair recipient cells. Even a short-term incubation of chemonaive with secretomes induces changes resembling those are observed chemoresistant patient-derived tumor long-term therapy. Using integrative omics techniques, find both enriched spliceosomal components, which relocalize from the nucleus cytoplasm subsequently into extracellular vesicles treatment. We demonstrate these substantially contribute phenotypic effects secretomes. Thus, SNU13 SYNCRIP proteins resistance, while exogenous U12 U6atac snRNAs stimulate growth. These findings significance network perturbation during further highlight signaling might be key factor contributing emergence resistance.

Language: Английский

Exploring extracellular RNA as drivers of chemotherapy resistance in cancer DOI

Yumna Khan,

Md Sadique Hussain, Prasanna Srinivasan Ramalingam

et al.

Molecular Biology Reports, Journal Year: 2025, Volume and Issue: 52(1)

Published: Jan. 21, 2025

Language: Английский

Citations

2
From Crypts to Cancer: A Holistic Perspective on Colorectal Carcinogenesis and Therapeutic Strategies DOI Open Access
Ehsan Gharib, Gilles A. Robichaud

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(17), P. 9463 - 9463

Published: Aug. 30, 2024

Colorectal cancer (CRC) represents a significant global health burden, with high incidence and mortality rates worldwide. Recent progress in research highlights the distinct clinical molecular characteristics of colon versus rectal cancers, underscoring tumor location's importance treatment approaches. This article provides comprehensive review our current understanding CRC epidemiology, risk factors, pathogenesis, management strategies. We also present intricate cellular architecture colonic crypts their roles intestinal homeostasis. carcinogenesis multistep processes are described, covering conventional adenoma-carcinoma sequence, alternative serrated pathways, influential Vogelstein model, which proposes sequential

Language: Английский

Citations

9
Molecular Imaging of Cancer Stem Cells and Their Role in Therapy Resistance DOI Creative Commons
Sofia Nascimento dos Santos, Timothy H. Witney

Journal of Nuclear Medicine, Journal Year: 2025, Volume and Issue: 66(1), P. 14 - 19

Published: Jan. 1, 2025

Despite recent therapeutic breakthroughs, cancer patients continue to face high recurrence and mortality rates due treatment resistance. Cancer stem cells (CSCs), a subpopulation with self-renewal capabilities, are key drivers of refractive disease. This review explores the application molecular imaging techniques, such as PET SPECT, for noninvasive detection CSCs. By providing real-time monitoring CSCs, these methods have potential predict therapy resistance guide personalized approaches. Here, we cover biological characteristics mechanisms resistance, identification targeting CSC-specific biomarkers imaging. Additionally, address challenges opportunities clinical translation CSC imaging, highlighting strategies where can be used improve patient outcomes.

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
Integrated Bioinformatic Analyses Reveal Thioredoxin as a Putative Marker of Cancer Stem Cells and Prognosis in Prostate Cancer DOI Creative Commons

Shigeru Sugiki,

Tetsuhiro Horie,

Kenshiro Kunii

et al.

Cancer Informatics, Journal Year: 2025, Volume and Issue: 24

Published: Jan. 1, 2025

Objectives: Prostate cancer stem cells (CSCs) play an important role in cell survival, proliferation, metastasis, and recurrence; thus, removing CSCs is for complete removal. However, the mechanisms underlying CSC functions remain largely unknown, making it difficult to develop new anticancer drugs targeting CSCs. Herein, we aimed identify novel factors that regulate stemness predict prognosis. Methods: We reanalyzed 2 single-cell RNA sequencing data of prostate (PCa) tissues using Seurat. used gene set enrichment analysis (GSEA) estimate identified common upregulated genes between these datasets. To investigate whether its expression levels change over differentiation, performed a trajectory monocle 3. In addition, GSEA helped us understand how stemness. Finally, assess their clinical significance, Cancer Genome Atlas database evaluate impact on Results: The thioredoxin ( TXN), redox enzyme, was approximately 1.2 times higher than PCa P < 1 × 10 −10 ), TXN decreased differentiation. suggested intracellular signaling pathways, including MYC, may be involved regulation by TXN. Furthermore, correlated with poor prognosis (P .05) patients high Conclusions: Despite limited sample size our study need further vitro vivo experiments demonstrate functionally regulates CSCs, findings suggest serve as therapeutic target against Moreover, could useful marker predicting patients.

Language: Английский

Citations

1
Recent Advancements of Aptamers in Cancer Therapy DOI Creative Commons

Swathi Venkatesan,

Kaushik Chanda,

M. M. Balamurali

et al.

ACS Omega, Journal Year: 2023, Volume and Issue: 8(36), P. 32231 - 32243

Published: Aug. 30, 2023

Aptamers are chemical antibodies possessing the capability of overcoming limitations posed by conventional antibodies, particularly for diagnostic, therapeutic, and theranostic applications in cancer. The ease modifications or functionalization, including conjugations with nucleic acids, drug molecules, nanoparticles, has made these aptamers to gain priorities research. In this Mini-review, various reports on therapeutics aptamer-functionalized nanomaterials controlled multistep release, targeted delivery, stimuli-responsive etc. discussed. case nucleic-acid-conjugated aptamers, DNA nanotrains beacons discussed terms possibility multidrug loading chemotherapy gene therapy. Developments electrochemical aptasensors signal-enhanced immune also Further, future scope aptamer technology cancer theranostics prevailing

Language: Английский

Citations

20
lncRNAs: New players of cancer drug resistance via targeting ABC transporters DOI

Mohammad Ebrahimnezhad,

Sanaz Hassanzadeh Asl,

Maede Rezaie

et al.

IUBMB Life, Journal Year: 2024, Volume and Issue: 76(11), P. 883 - 921

Published: Aug. 1, 2024

Cancer drug resistance poses a significant obstacle to successful chemotherapy, primarily driven by the activity of ATP-binding cassette (ABC) transporters, which actively efflux chemotherapeutic agents from cancer cells, reducing their intracellular concentrations and therapeutic efficacy. Recent studies have highlighted pivotal role long noncoding RNAs (lncRNAs) in regulating this resistance, positioning them as crucial modulators ABC transporter function. lncRNAs, once considered transcriptional noise, are now recognized for complex regulatory capabilities at various cellular levels, including chromatin modification, transcription, post-transcriptional processing. This review synthesizes current research demonstrating how lncRNAs influence modulating expression transporters. can act molecular sponges, sequestering microRNAs that would otherwise downregulate genes. Additionally, they alter epigenetic landscape these genes, affecting activity. Mechanistic insights reveal contribute thereby altering drugs promoting resistance. Understanding interactions provides new perspective on basis chemoresistance, emphasizing network knowledge not only deepens our understanding biological mechanisms underlying but also suggests novel strategies. In conclusion, intricate interplay between transporters is developing innovative solutions combat underscoring importance continued field.

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
The Enigma of Cancer Polyploidy as Deciphered by Evolutionary Cancer Cell Biology (ECCB) DOI Open Access
Vladimir F. Niculescu,

Eugenia Niculescu

Published: Feb. 29, 2024

Evolutionary Cancer Cell Biology (ECCB) reveals that the majority of cancer hallmarks trace their origins back to premetazoic era, approximately 2300 1750 million years ago. These share deep homology with oxygen-sensitive non-gametogenic NG (Urgermline), which evolved from common ancestor Amoebozoan, Metazoan, and Fungi (AMF). The genes, gene modules, regulatory networks cell system are preserved in ancestral genome compartment metazoans humans. Urgermline serves as a blueprint for all germ stem lineages, including parasitic amoebae. As observed amoebae, DNA double-strand breaks (DSBs) manifest homologous recombination (HR) genes germlines lineages when exposed specific hyperoxic conditions, referred AMF hyperoxia, characterized by an oxygen content exceeding 6.0%. cells lose stemness differentiation potential but persist proliferation low-grade polyploids (4n) through defective symmetric division (DSCD phenotype). Genomic integrity can be restored homotypic nuclear fusion, resulting formation high-grade known multinuclear repair syncytia (MGRSs), or inductive hyperpolyploidization more than 64n, single-celled polyploid giant (PGCCs). Interestingly, low-, middle-, polyploidization not exclusive cancer. Therefore, we investigate (i) functional polyploidies occur healthy cells, humans, mammals, protists, (ii) dysfunctional impaired irreparable DSB defects, (iii) restoration cyst-like events. Additionally, explore dysfunction aging hepatocytes, cardiomyocytes

Language: Английский

Citations

5
Mechanisms of Cancer Resistance to Various Therapies DOI
Asiya Batool,

Waseem Rashid,

Kaneez Fatima

et al.

Published: Jan. 1, 2024

Cancer therapy has witnessed remarkable advancements in eradicating cancer cells within the body, leading to improved patient outcomes and prolonged survival. This chapter provides an overview of current therapies, encompassing radiation therapy, chemotherapy, targeted immunotherapy, emerging therapeutic modalities such as viral gene therapy. explores intricate molecular mechanisms underpinning resistance discusses contemporary approaches designed combat against immunotherapy. In conclusion, evolved significantly, offering diverse treatment options. Continued research, clinical trials, multidisciplinary collaboration are essential for further refining optimizing quality life. Understanding developing innovative strategies crucial enhancing outcomes, making ongoing research trials indispensable.

Language: Английский

Citations

5