Genomic and Epigenomic Aberrations in Esophageal Squamous Cell Carcinoma and Implications for Patients

Lin, De–Chen; Wang, Ming-Rong; Koeffler, H. Phillip

doi:10.1053/j.gastro.2017.06.066

Cited by 200 publications

(156 citation statements)

References 142 publications

(137 reference statements)

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“…ESCC is common (more than 400,000 cases each year) and aggressive malignancy (causing almost 300,000 deaths per year), with a 5-year survival rate less than 20% Enzinger and Mayer, 2003). Unfortunately, genome-guided therapeutic strategy is still unavailable for ESCC patients, although ESCC genomic abnormalities have been comprehensively characterized and established (Cancer Genome Atlas Research et al, 2017;Gao et al, 2014;Lin et al, 2018a;Lin et al, 2014;Lin et al, 2018b;Liu et al, 2017;Song et al, 2014). In addition, the high-degree genomic heterogeneity of this cancer further limits application of mutational-targeted therapy.…”

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confidence: 99%

TP63, SOX2 and KLF5 Establish Core Regulatory Circuitry and Construct Cancer Specific Epigenome in Esophageal Squamous Cell Carcinoma

Jiang

et al. 2019

Preprint

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novel CRC target contributing to ESCC viability. Using circular chromosome conformation capture sequencing (4C-seq) and CRISPR/Cas9 genome editing, the direct interaction between TP63 promoter and functional enhancers which is mediated by CRC TFs is identified. Deletion of each enhancer decreases expression of CRC TFs and impairs cell viability, phenocopying the knockdown of each CRC TF.Targeting epigenetic regulation by inhibition of either the BET bromodomain or HDAC disrupts the CRC program and its dependent global epigenetic modification, consequently suppressing ESCC tumor growth. Importantly, combination of both compounds result in synergistic anti-tumor effect.

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confidence: 99%

TP63, SOX2 and KLF5 Establish Core Regulatory Circuitry and Construct Cancer Specific Epigenome in Esophageal Squamous Cell Carcinoma

Jiang

et al. 2019

Preprint

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“…A recent review article highlighted WES of ESCCs that revealed many crucial driver mutations and also mentioned WES for elucidating inter‐ and intratumor heterogeneity. This article also discusses the epigenetic alterations in ESCC emphasizing a major challenge of understanding epigenetic mechanisms contributing to carcinogenesis . A couple of studies summarized and re‐analyzed the genomic data from several recent genomic studies of large cohorts of ESCC patients .…”

Section: Genomics Mutations and Deregulated Pathwaysmentioning

confidence: 99%

“…This article also discusses the epigenetic alterations in ESCC emphasizing a major challenge of understanding epigenetic mechanisms contributing to carcinogenesis. 31 A couple of studies summarized and re-analyzed the genomic data from several recent genomic studies of large cohorts of ESCC patients. 32,33 The re-analysis by Du et al identified recurrent mutations in approximately 18 genes, 15 of which had been reported previously (TP53, AJUBA, CDKN2A, KMT2D (MLL2), ZNF750, FAT1, NOTCH1, NOTCH3, PIK3CA, NFE2L2, RB1, KDM6A, FBXW7, CREBBP, and TGFBR2), with three significantly mutated novel genes (CUL3, PTEN, and DCDC1).…”

Section: Genomics Mutations and Deregulated Pathwaysmentioning

confidence: 99%

Molecular landscape of esophageal cancer: implications for early detection and personalized therapy

Talukdar

Pietro

Secrier

et al. 2018

Annals of the New York Academy of Sciences

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Esophageal cancer (EC) is one of the most lethal cancers and a public health concern worldwide, owing to late diagnosis and lack of efficient treatment. Esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) are main histopathological subtypes of EC that show striking differences in geographical distribution, possibly due to differences in exposure to risk factors and lifestyles. ESCC and EAC are distinct diseases in terms of cell of origin, epidemiology, and molecular architecture of tumor cells. Past efforts aimed at translating potential molecular candidates into clinical practice proved to be challenging, underscoring the need for identifying novel candidates for early diagnosis and therapy of EC. Several major international efforts have brought about important advances in identifying molecular landscapes of ESCC and EAC toward understanding molecular mechanisms and critical molecular events driving the progression and pathological features of the disease. In our review, we summarize recent advances in the areas of genomics and epigenomics of ESCC and EAC, their mutational signatures and immunotherapy. We also discuss implications of recent advances in characterizing the genome and epigenome of EC for the discovery of diagnostic/prognostic biomarkers and development of new targets for personalized treatment and prevention.

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“…Alcohol intake and tobacco use are responsible for at least 75% of these carcinomas. The underlying initiation and progression mechanisms of OSCC and ESCC are generally characterized by the accumulation of serial epigenetic and genetic alterations, which eventually lead to uncontrolled proliferation of the mutated cells, followed by vigorous cell division . Early‐stage OSCC detection displays an 80% survival rate at 5 years, while detection at advanced stage leads to survival rates ranging from 20% to 40% .…”

Section: Introductionmentioning

confidence: 99%

Autophagy modulators for the treatment of oral and esophageal squamous cell carcinomas

Khan

Relitti

Brindisi

et al. 2019

Medicinal Research Reviews

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Oral squamous cell carcinomas (OSCC) and esophageal squamous cell carcinomas (ESCC) exhibit a survival rate of less than 60% and 40%, respectively. Late-stage diagnosis and lack of effective treatment strategies make both OSCC and ESCC a significant health burden. Autophagy, a lysosome-dependent catabolic process, involves the degradation of intracellular components to maintain cell homeostasis. Targeting autophagy has been highlighted as a feasible therapeutic strategy with clinical utility in cancer treatment, although its associated regulatory mechanisms remain elusive. The detection of relevant biomarkers in biological fluids has been anticipated to facilitate early diagnosis and/or prognosis for these tumors. In this context, recent studies have indicated the presence of specific proteins and small RNAs, detectable in circulating plasma and serum, as biomarkers. Interestingly, the interplay between biomarkers (eg, exosomal microRNAs) and autophagic processes could be exploited in the quest for targeted and more effective therapies for OSCC and ESCC. In this review, we give an overview of the available biomarkers and innovative targeted therapeutic strategies, including the application of autophagy modulators in OSCC and ESCC.Additionally, we provide a viewpoint on the state of the art Tuhina Khan and Nicola Relitti contributed equally to this work. and on future therapeutic perspectives combining the early detection of relevant biomarkers with drug discovery for the treatment of OSCC and ESCC. K E Y W O R D S autophagy, autophagy modulators, biomarkers, esophageal squamous cell carcinoma, exosomes, oral squamous cell carcinoma, targeted therapy 1 | INTRODUCTION Oral squamous cell carcinoma (OSCC) is the predominant malignant neoplasm of the oral cavity followed by verrucous carcinoma, undifferentiated carcinoma, and small salivary adenocarcinoma. 1 Esophageal squamous cell carcinoma (ESCC) is the first histological type and accounts for 80% of cases of esophageal cancer. 2 OSCC and ESCC are indicated as one of the most common cancers by the International Union Against Cancer with an annual incidence of 275 000 and 456 000 cases worldwide, respectively. 3,4 The primary etiology in both OSCC and ESCC is attributed to the environmental factors (tobacco abuse, alcohol consumption), genetic factors (eg, mutations in enzymes), viral factors (human papilloma virus [HPV] infection), and/or the coexistence of these factors. Alcohol intake and tobacco use are responsible for at least 75% of these carcinomas. The underlying initiation and progression mechanisms of OSCC and ESCC are generally characterized by the accumulation of serial epigenetic and genetic alterations, which eventually lead to uncontrolled proliferation of the mutated cells, followed by vigorous cell division. 5,7 Early-stage OSCC detection displays an 80% survival rate at 5 years, while detection at advanced stage leads to survival rates ranging from 20% to 40%. 6 In ESCC, the 5-year survival rate for early-stage detection may reach 85%, whereas a dr...

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Genomic and Epigenomic Aberrations in Esophageal Squamous Cell Carcinoma and Implications for Patients

Cited by 200 publications

References 142 publications

TP63, SOX2 and KLF5 Establish Core Regulatory Circuitry and Construct Cancer Specific Epigenome in Esophageal Squamous Cell Carcinoma

TP63, SOX2 and KLF5 Establish Core Regulatory Circuitry and Construct Cancer Specific Epigenome in Esophageal Squamous Cell Carcinoma

Molecular landscape of esophageal cancer: implications for early detection and personalized therapy

Autophagy modulators for the treatment of oral and esophageal squamous cell carcinomas

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