Early development of esophageal squamous cell cancer: Stem cells, cellular origins and early clone evolution

Liao, Guobin; Tang, Jun; Bai, Jianying

doi:10.1016/j.canlet.2022.216047

Cited by 6 publications

(4 citation statements)

References 91 publications

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“…Given that ncRNAs can regulate the expression of downstream target genes through multiple mechanisms, future considerations may involve combining ncRNA-targeted therapy with existing targeted drugs for ESCC. This approach could involve the synergistic regulation of key genes in ESCC progression, such as Notch1, EGFR and human epidermal growth factor receptor 2 (170)(171)(172). In addition, the regulatory effects of ncRNAs on multiple immune checkpoints have been confirmed and a potential combination of ncRNA-targeted therapy with immunotherapy could be trialed for ESCC in future studies (173,174).…”

Section: Discussionmentioning

confidence: 99%

Non‑coding RNA: A promising diagnostic biomarker and therapeutic target for esophageal squamous cell carcinoma (Review)

Zhang,

Wang,

Gao

et al. 2024

Oncol Lett

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Esophageal cancer (EC) is a common form of malignant tumor in the digestive system that is classified into two types: Esophageal squamous cell carcinomas (ESCC) and esophageal adenocarcinoma. ESCC is known for its early onset of symptoms, which can be difficult to identify, as well as its rapid progression and tendency to develop drug resistance to chemotherapy and radiotherapy. These factors contribute to the high incidence of disease and low cure rate. Therefore, a diagnostic biomarker and therapeutic target need to be identified for ESCC. Non-coding RNAs (ncRNAs) are a class of molecules that are transcribed from DNA but do not encode proteins. Initially, ncRNAs were considered to be non-functional segments generated during transcription. However, with advancements in high-throughput sequencing technologies in recent years, ncRNAs have been associated with poor prognosis, drug resistance and progression of ESCC. The present study provides a comprehensive overview of the biogenesis, characteristics and functions of ncRNAs, particularly focusing on microRNA, long ncRNAs and circular RNAs. Furthermore, the ncRNAs that could potentially be used as diagnostic biomarkers and therapeutic targets for ESCC are summarized to highlight their application value and prospects in ESCC.

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Section: Discussionmentioning

confidence: 99%

Non‑coding RNA: A promising diagnostic biomarker and therapeutic target for esophageal squamous cell carcinoma (Review)

Zhang,

Wang,

Gao

et al. 2024

Oncol Lett

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“…Regarding cancer cell plasticity, epigenetic changes seem to be involved in the regulation of tumor microenvironment, which influences the continuous transition of tumor cells from stem to non-stem cancer cells, from an active to a quiescent state, and from an epithelial to a mesenchymal status. This behavior is well known in the case of epithelial tumors, but it is insufficiently investigated in the specific case of cSCC [ 84 , 85 ].…”

Section: Tumor Heterogeneity: Cancer Stem Cells and Therapy Resistancementioning

confidence: 99%

Update on the Molecular Pathology of Cutaneous Squamous Cell Carcinoma

Cozma

Banciu

Soare

et al. 2023

IJMS

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Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer, originating from keratinocytes of the spinous layer. Numerous risk factors have been discovered for the initiation and growth of this type of cancer, such as exposure to UV and ionizing radiation, chemical carcinogens, the presence of immunosuppression states, chronic inflammation, infections with high-risk viral strains, and, last but not least, the presence of diseases associated with genetic alterations. The important socio-economic impact, as well as the difficulty associated with therapy for advanced forms, has made the molecular mechanisms underlying this neoplasia more and more intensively studied, with the intention of achieving a better understanding and advancing the treatment of this pathology. This review aims to provide a brief foray into the molecular, genetic, and epigenetic aspects of this cancer, as well as the treatment methods, ranging from the first used to the latest targeted therapies.

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“…Specifically, mutations that result in a reduction or loss of NOTCH1 function are thought to increase cell fitness: nonsense and essential splice mutations are under especially strong positive selection in normal esophageal epithelia (22,23). The result of strong positive selection of NOTCH1 mutants in normal tissue may be a reduced competitive advantage in tumor cells (24). Indeed, a recent study in mice demonstrated that mutation of NOTCH1 in normal esophageal tissue caused clonal expansion, but impaired tumor growth (25).…”

Section: Introductionmentioning

confidence: 99%

Mutation of NOTCH1 is selected within normal esophageal tissues, yet leads to selective epistasis suppressive of further evolution into cancer

Glasmacher,

Cannataro,

Mandell

et al. 2023

Preprint

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Sequencing of tissues from histologically normal esophagus, among other organs, has revealed that normal tissues harbor somatic variants that are also found in cancers arising from the same tissue types. Our understanding of how somatic mutations commonly found in normal tissue can contribute to tumorigenesis is limited: common somatic mutations may or may not confer phenotypes compatible with oncogenesis. However, the strength of selection for somatic variants that appear in both normal and cancer tissues can be quantified in each context using evolutionary modeling approaches. We studied the evolutionary trajectory from normal esophageal tissue to esophageal squamous-cell carcinoma (ESCC) by analysis of 2171 sequenced samples from previous studies on normal esophageal epithelium and ESCC to reveal the stepwise contributions of somatic mutations to increased cellular division and survival. We also analyzed pairwise selective epistasis between somatically mutated genes that may lead to stepwise substitution patterns. We found thatNOTCH1substitutions are highly selected along the trajectory from embryogenesis to adult normal esophageal tissue, explaining their high prevalence in the tissue. In contrast, there is little to no positive selection forNOTCH1mutations along the trajectory from adult normal tissue to ESCC, suggesting thatNOTCH1substitutions do not drive tumorigenesis. Furthermore, mutations in NOTCH1 exhibit antagonistic epistasis with well-known cancer drivers including TP53, reducing selection for progressive mutations in tumorigenesis. This antagonistic epistasis likely corresponds with a low likelihood of tumor progression in the presence ofNOTCH1mutations in the esophagus.

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Early development of esophageal squamous cell cancer: Stem cells, cellular origins and early clone evolution

Cited by 6 publications

References 91 publications

Non‑coding RNA: A promising diagnostic biomarker and therapeutic target for esophageal squamous cell carcinoma (Review)

Non‑coding RNA: A promising diagnostic biomarker and therapeutic target for esophageal squamous cell carcinoma (Review)

Update on the Molecular Pathology of Cutaneous Squamous Cell Carcinoma

Mutation of NOTCH1 is selected within normal esophageal tissues, yet leads to selective epistasis suppressive of further evolution into cancer

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