The progress and challenges in modeling colorectal cancer and the impact on novel drug discovery DOI
Natália Teixeira, Ana Baião, Sofia Dias

et al.

Expert Opinion on Drug Discovery, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 10

Published: Sept. 16, 2024

Colorectal cancer (CRC) remains one of the leading causes cancer-related morbidity and mortality worldwide. This disease is complex heterogeneous, influenced by a variety genetic, epigenetic, environmental factors that drive CRC initiation progression. Despite advances in therapeutic strategies, five-year survival rate for metastatic alarmingly low. Traditional two-dimensional (2D) cell culture systems have been foundation research, but their inability to replicate tumor microenvironment (TME) limits effectiveness.

Language: Английский

Exploring the Anti-Colon Cancer Potential of Polygonum minus: Integrating In Vitro and In Silico Studies DOI
Zhongming Yang, Zhongguo Yang,

Md Zuki Abu Bakar

et al.

Food Bioscience, Journal Year: 2025, Volume and Issue: 64, P. 105853 - 105853

Published: Jan. 6, 2025

Language: Английский

Citations

3
tRNA-derived small RNAs: their role in the mechanisms, biomarkers, and therapeutic strategies of colorectal cancer DOI Creative Commons
Bo Zhang, Yi Pan, Zhe Li

et al.

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: Jan. 13, 2025

Colorectal cancer (CRC) is the third most prevalent malignancy and second leading cause of cancer-related mortality worldwide, with an increasing shift towards younger age onset. In recent years, there has been recognition significance tRNA-derived small RNAs (tsRNAs), encompassing fragments (tRFs) tRNA halves (tiRNAs). Their involvement in regulating translation, gene expression, reverse transcription, epigenetics gradually come to light. Emerging research revealed dysregulation tsRNAs CRC, implicating their role CRC initiation progression, highlighting potential early diagnosis, prognosis, therapeutic strategies. Although clinical application still its stages, findings highlight a close relationship between biogenesis function tsRNAs, chemical modifications, tumor immune microenvironment (TIME). Additionally, similar other RNAs, can be effectively delivered via nanoparticles (NPs). Consequently, future should focus on elucidating concerning base TIME regulation, immunotherapy, NPs delivery systems facilitate translation.

Language: Английский

Citations

1
Dark force rising: Reawakening and targeting of fetal-like stem cells in colorectal cancer DOI Creative Commons
Sigrid K. Fey,

Nuria Vaquero‐Siguero,

René Jackstadt

et al.

Cell Reports, Journal Year: 2024, Volume and Issue: 43(6), P. 114270 - 114270

Published: May 23, 2024

Stem cells play pivotal roles in maintaining intestinal homeostasis, orchestrating regeneration, and key steps of colorectal cancer (CRC) initiation progression. Intriguingly, adult stem are reduced during many these processes. On the contrary, primitive fetal programs, commonly detected development, emerge tissue repair, CRC metastasis, therapy resistance. Recent findings indicate a dynamic continuum between cell programs. We discuss critical mechanisms facilitating plasticity states highlight heterogeneity observed upon appearance fetal-like states. focus on therapeutic opportunities that arise by targeting how those concepts can be translated into clinic.

Language: Английский

Citations

4
Navigating beyond associations: Opportunities to establish causal relationships between the gut microbiome and colorectal carcinogenesis DOI
Floor S Baas, Nele Brusselaers, Irıs D. Nagtegaal

et al.

Cell Host & Microbe, Journal Year: 2024, Volume and Issue: 32(8), P. 1235 - 1247

Published: Aug. 1, 2024

Language: Английский

Citations

4
Mutation Analysis of TMB‐High Colorectal Cancer: Insights Into Molecular Pathways and Clinical Implications DOI Creative Commons

Yuko Chikaishi,

Hiroshi Matsuoka, Eiji Sugihara

et al.

Cancer Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 16, 2025

ABSTRACT Colorectal cancer (CRC) is well characterized in terms of genetic mutations and the mechanisms by which they contribute to carcinogenesis. Mutations APC , TP53 KRAS are common CRC, indicating key roles for these genes tumor development progression. However, certain tumors with low frequencies that defined location molecular phenotypes, a carcinogenic mechanism dependent on BRAF has been proposed. We here analyzed targeted sequence data linked clinical information focusing high mutation burden (TMB) order identify characteristics associated mutations, their relations features, carcinogenesis lacking major driver oncogenes. Analysis overall confirmed were most prevalent our cohort. Compared other tumors, TMB‐high more frequent right side colon, had lower higher as microsatellite instability (MSI) score, showed greater contribution mutational signature MSI. Ranking variant allele play role early suggested related DNA damage response (such ATM POLE ) MSI MSH2 MSH6 may precede activation serrated pathway tumors. Our results thus indicate suggest mismatch repair CRC.

Language: Английский

Citations

0
Mouse colorectal cancer organoids: lessons from syngeneic and orthotopic transplantation systems DOI Creative Commons
Yu Muta, Yuki Nakanishi

European Journal of Cell Biology, Journal Year: 2025, Volume and Issue: 104(2), P. 151478 - 151478

Published: Feb. 6, 2025

Colorectal cancer (CRC) organoids provide more accurate and tissue-relevant models compared to conventional two-dimensional cultured cell cultures. Mouse CRC organoids, in particular, offer unique advantages over their human counterparts, as they can be transplanted into immunocompetent mice. These syngeneic transplantation create a robust system for studying biology the tumor microenvironment (TME). This article discusses development applications of these organoid systems, emphasizing capacity faithfully recapitulate vivo progression, metastasis, immune landscape.

Language: Английский

Citations

0
Organoid models: applications and research advances in colorectal cancer DOI Creative Commons

Yijie Wu,

Sha Yu,

Xingpo Guo

et al.

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 15

Published: Feb. 7, 2025

This review summarizes the applications and research progress of organoid models in colorectal cancer research. First, high incidence mortality rates are introduced, emphasizing importance organoids as a model. Second, this provides detailed introduction to concept, biological properties, organoids, including their strengths mimicking structural functional aspects organs. article further analyzes adult stem cell-derived pluripotent discusses advancements for basic research, drug development, personalized treatment evaluation prediction, regenerative medicine. Finally, prospects applying technology its significant value improving patient survival rates. In conclusion, systematically explains highlighting tremendous potential promising

Language: Английский

Citations

0
Early immune evasion in colorectal cancer: interplay between stem cells and the tumor microenvironment DOI

Norihiro Goto,

Judith Agudo,

Ömer H. Yilmaz

et al.

Trends in cancer, Journal Year: 2025, Volume and Issue: unknown

Published: May 1, 2025

Language: Английский

Citations

0
Origin, development and therapy of colorectal cancer from the perspective of a biologist and an oncologist DOI Creative Commons
Jiří Švec, Jakub Onhajzer, Vladimír Kořínek

et al.

Critical Reviews in Oncology/Hematology, Journal Year: 2024, Volume and Issue: 204, P. 104544 - 104544

Published: Oct. 25, 2024

The intestinal epithelium, a rapidly renewing tissue, is characterized by continuous cell turnover that occurs through well-coordinated process of proliferation and differentiation. This dynamic crucial for the long-term function gastrointestinal tract. Disruption this can lead to colorectal carcinoma, common malignancy worldwide. first part review focuses on cellular composition epithelium molecular mechanisms control its functions, describes pathways epithelial transformation tumor progression. forms basis understanding development progression advanced cancer. second deals with current therapeutic approaches presents latest treatment options, ongoing clinical trials new drugs. In addition, biological medical perspectives adverse effects therapies models regeneration are highlighted and, finally, future options discussed.

Language: Английский

Citations

2
TGFβ-Responsive Stromal Activation Occurs Early in Serrated Colorectal Carcinogenesis DOI Open Access

Hideaki Tsumuraya,

Hirokazu Okayama,

Masanori Katagata

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(9), P. 4626 - 4626

Published: April 24, 2024

Activated TGFβ signaling in the tumor microenvironment, which occurs independently of epithelial cancer cells, has emerged as a key driver progression late-stage colorectal (CRC). This study aimed to elucidate contribution TGFβ-activated stroma serrated carcinogenesis, representing approximately 25% CRCs and often characterized by oncogenic BRAF mutations. We used transcriptional signature developed based on TGFβ-responsive, stroma-specific genes infer TGFβ-dependent stromal activation conducted silico analyses 3 single-cell RNA-seq datasets from total 39 CRC samples 12 bulk transcriptomic consisting 2014 416 precursor samples, 33 were lesions. Single-cell validated that was expressed specifically effectively excluding signals derived cells. found upregulated during malignant transformation progression, it particularly enriched with mutant compared wild-type counterparts. Furthermore, across four independent datasets, lesions exhibited significantly higher levels TGFβ-responsive conventional adenomas. large-scale analysis suggests early carcinogenesis. Our provides novel insights into molecular mechanisms underlying development via pathway.

Language: Английский

Citations

1