Tumor initiation and early tumorigenesis: molecular mechanisms and interventional targets

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: June 18, 2024

Abstract Tumorigenesis is a multistep process, with oncogenic mutations in normal cell conferring clonal advantage as the initial event. However, despite pervasive somatic and expansion tissues, their transformation into cancer remains rare event, indicating presence of additional driver events for progression to an irreversible, highly heterogeneous, invasive lesion. Recently, researchers are emphasizing mechanisms environmental tumor risk factors epigenetic alterations that profoundly influencing early malignant evolution, independently inducing mutations. Additionally, evolution tumorigenesis reflects multifaceted interplay between cell-intrinsic identities various cell-extrinsic exert selective pressures either restrain uncontrolled proliferation or allow specific clones progress tumors. by which induce both intrinsic cellular competency remodel stress facilitate not fully understood. In this review, we summarize genetic, epigenetic, external events, effects on co-evolution transformed cells ecosystem during initiation evolution. A deeper understanding earliest molecular holds promise translational applications, predicting individuals at high-risk developing strategies intercept transformation.

Language: Английский

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Esophageal cancer screening, early detection and treatment: Current insights and future directions

World Journal of Gastrointestinal Oncology, Journal Year: 2024, Volume and Issue: 16(4), P. 1180 - 1191

Published: April 9, 2024

Esophageal cancer ranks among the most prevalent malignant tumors globally, primarily due to its highly aggressive nature and poor survival rates. According 2020 global statistics, there were approximately 604000 new cases of esophageal cancer, resulting in 544000 deaths. The 5-year rate hovers around a mere 15%-25%. Notably, distinct variations exist risk factors associated with two primary histological types, influencing their worldwide incidence distribution. Squamous cell carcinoma displays high specific regions, such as certain areas China, where it meets cost-effectiveness criteria for widespread endoscopy-based early diagnosis within local population. Conversely, adenocarcinoma (EAC) represents common subtype Europe United States. role EAC originating from Barrett's esophagus (BE) remains subject controversy. effectiveness detection EAC, particularly those arising BE, continues be debated topic. how early-stage is treated different regions are largely differing rates diagnoses. In higher incidences, China Japan, more common, which has led advancement endoscopic methods definitive treatments. These techniques have demonstrated remarkable efficacy minimal complications while preserving functionality. Early screening, prompt diagnosis, timely treatment key strategies that can significantly lower both occurrence death cancer.

Language: Английский

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Spatial immune scoring system predicts hepatocellular carcinoma recurrence

Nature, Journal Year: 2025, Volume and Issue: unknown

Published: March 12, 2025

Language: Английский

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Aberrant epithelial cell interaction promotes esophageal squamous-cell carcinoma development and progression

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Dec. 15, 2023

Abstract Epithelial-mesenchymal transition (EMT) and proliferation play important roles in epithelial cancer formation progression, but what molecules how they trigger EMT is largely unknown. Here we performed spatial transcriptomic functional analyses on samples of multistage esophageal squamous-cell carcinoma (ESCC) from mice humans to decipher these critical issues. By investigating spatiotemporal gene expression patterns cell–cell interactions, demonstrated that the aberrant cell interaction via EFNB1-EPHB4 triggers cycle mediated by downstream SRC/ERK/AKT signaling. The occurs within basal layer at early precancerous lesions, which expands whole strengthens along development progression. Functional analysis revealed caused overexpressed ΔNP63 due TP53 mutation, culprit human ESCC tumorigenesis. Our results shed new light role TP53-TP63/ΔNP63-EFNB1-EPHB4 axis formation.

Language: Английский

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Squamous cell cancers of the aero-upper digestive tract: A unified perspective on biology, genetics, and therapy

Cancer Cell, Journal Year: 2025, Volume and Issue: 43(2), P. 178 - 194

Published: Feb. 1, 2025

Language: Английский

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Single-cell multi-stage spatial evolutional map of esophageal carcinogenesis

Cancer Cell, Journal Year: 2025, Volume and Issue: 43(3), P. 380 - 397.e7

Published: March 1, 2025

Cancer development involves the co-evolution of cancer cells and their surrounding microenvironment, yet dynamics this interaction within physical architecture remains poorly understood. Here, we present a spatial transcriptomic map at single-cell resolution, encompassing 127 multi-stage fields view from 43 patients, to chart evolutionary trajectories human esophageal squamous cell carcinoma (ESCC). By analyzing 6.4 million cells, reveal that ESCC progression is driven by proliferative epithelial subpopulation acquires dedifferentiated invasive characteristics. At late precancerous stage, these disrupt epithelial-stromal interface recruit normal fibroblasts via JAG1-NOTCH1 signaling, transforming them into cancer-associated (CAFs). This leads formation "CAF-Epi" (CAF cell) niche tumor edge shields immune surveillance. The CAF-Epi key indicator in other carcinomas patient outcomes.

Language: Английский

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Emerging strategies to investigate the biology of early cancer

Nature reviews. Cancer, Journal Year: 2024, Volume and Issue: 24(12), P. 850 - 866

Published: Oct. 21, 2024

Language: Английский

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APOBEC Mutagenesis in Cancer Development and Susceptibility

Cancers, Journal Year: 2024, Volume and Issue: 16(2), P. 374 - 374

Published: Jan. 15, 2024

APOBEC cytosine deaminases are prominent mutators in cancer, mediating mutations over 50% of cancers. mutagenesis has been linked to tumor heterogeneity, persistent cell evolution, and therapy responses. While emerging evidence supports the impact on cancer progression, understanding its contribution susceptibility malignant transformation is limited. We examine existing for role carcinogenesis basis reported associations between germline polymorphisms genes encoding enzymes risk, insights into activities from sequencing efforts both non-malignant human tissues, vivo studies. discuss key knowledge gaps highlight possible ways gain a deeper development.

Language: Английский

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Identification of a gene score related to antigen processing and presentation machinery for predicting prognosis in head and neck squamous cell carcinoma and its potential implications for immunotherapy

Clinical & Translational Oncology, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 31, 2024

Language: Английский

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Cancer evolution: from Darwin to the Extended Evolutionary Synthesis

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

Published: Jan. 1, 2025

The fundamental evolutionary nature of cancer has been recognized for decades. Increasingly powerful genetic and single cell sequencing technologies, as well preclinical models, continue to unravel the evolution premalignant cells, progression metastatic stages drug-resistant end-stage disease. Here, we summarize recent advances distil principles their relevance clinic. We reveal how microenvironmental plasticity are intertwined with Darwinian demonstrate need a conceptual framework that integrates these processes. This warrants adoption recently developed Extended Evolutionary Synthesis (EES).

Language: Английский

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