Epigenetics and Precision Oncology

Werner, Rachael J.; Kelly, Andrew D.; Issa, Jean–Pierre J.

doi:10.1097/ppo.0000000000000281

Cited by 77 publications

(56 citation statements)

References 66 publications

(78 reference statements)

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“…It is known that tumor aneuploidy (chromosome number variation) and genetic heterogeneity/diversity can influence the disease behavior including metastatic capability [190–192]. Apart from genetic changes, epigenetic alterations such as DNA methylation and histone modifications could play a significant role in metastasis [193,194]. Accumulating evidence suggests that both genetic and epigenetic changes can occur in obesity [195–199].…”

Section: Leptin In Tumor Progressionmentioning

confidence: 99%

The potential role of leptin in tumor invasion and metastasis

Ray

Cleary

2017

Cytokine & Growth Factor Reviews

114

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The adipocyte-released hormone-like cytokine/adipokine leptin behaves differently in obesity compared to its functions in the normal healthy state. In obese individuals, elevated leptin levels act as a pro-inflammatory adipokine and are associated with certain types of cancers. Further, a growing body of evidence suggests that higher circulating leptin concentrations and/or elevated expression of leptin receptors (Ob-R) in tumors may be poor prognostic factors. Although the underlying pathological mechanisms of leptin’s association with poor prognosis are not clear, leptin can impact the tumor microenvironment in several ways. For example, leptin is associated with a number of biological components that could lead to tumor cell invasion and distant metastasis. This includes interactions with carcinoma-associated fibroblasts, tumor promoting effects of infiltrating macrophages, activation of matrix metalloproteinases, transforming growth factor-β signaling, etc. Recent studies also have shown that leptin plays a role in the epithelial-mesenchymal transition, an important phenomenon for cancer cell migration and/or metastasis. Furthermore, leptin’s potentiating effects on insulin-like growth factor-I, epidermal growth factor receptor and HER2/neu have been reported. Regarding unfavorable prognosis, leptin has been shown to influence both adenocarcinomas and squamous cell carcinomas. Features of poor prognosis such as tumor invasion, lymph node involvement and distant metastasis have been recorded in several cancer types with higher levels of leptin and/or Ob-R. This review will describe the current scenario in a precise manner. In general, obesity indicates poor prognosis in cancer patients.

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Section: Leptin In Tumor Progressionmentioning

confidence: 99%

The potential role of leptin in tumor invasion and metastasis

Ray

Cleary

2017

Cytokine & Growth Factor Reviews

114

View full text Add to dashboard Cite

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“…Preclinical studies suggested that both gene mutation and epigenetic inactivation of BRCA1 by promoter hypermethylation can cause protein down-regulation and subsequent sensitivity to PARP (Poly-ADP-ribose polymerase) inhibition [73,74]. Also, it is recognized that aberrant DNA methylation and changes in gene expression are correlated with the molecular subtypes of BC [9,75]. However, epigenetic studies in IBC are scarce.…”

Section: Epigenetic Alterations In Inflammatory and Non-inflammatory mentioning

confidence: 99%

Epigenetics in Inflammatory Breast Cancer: Biological Features and Therapeutic Perspectives

Faldoni

Rainho

Rogatto

2020

Cells

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Evidence has emerged implicating epigenetic alterations in inflammatory breast cancer (IBC) origin and progression. IBC is a rare and rapidly progressing disease, considered the most aggressive type of breast cancer (BC). At clinical presentation, IBC is characterized by diffuse erythema, skin ridging, dermal lymphatic invasion, and peau d’orange aspect. The widespread distribution of the tumor as emboli throughout the breast and intra- and intertumor heterogeneity is associated with its poor prognosis. In this review, we highlighted studies documenting the essential roles of epigenetic mechanisms in remodeling chromatin and modulating gene expression during mammary gland differentiation and the development of IBC. Compiling evidence has emerged implicating epigenetic changes as a common denominator linking the main risk factors (socioeconomic status, environmental exposure to endocrine disruptors, racial disparities, and obesity) with IBC development. DNA methylation changes and their impact on the diagnosis, prognosis, and treatment of IBC are also described. Recent studies are focusing on the use of histone deacetylase inhibitors as promising epigenetic drugs for treating IBC. All efforts must be undertaken to unravel the epigenetic marks that drive this disease and how this knowledge could impact strategies to reduce the risk of IBC development and progression.

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“…DNA methylation-based biomarkers are useful tools to be applied in cancer diagnosis and prognosis. They are also associated with the therapeutic response and guide treatment decisions for cancer patients [22,23].…”

Section: Introductionmentioning

confidence: 99%

Comprehensive Analysis of DNA Methylation and Prediction of Response to NeoadjuvantTherapy in Locally Advanced Rectal Cancer

Canto

Barros-Filho

Rainho

et al. 2020

Cancers

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The treatment for locally advanced rectal carcinomas (LARC) is based on neoadjuvant chemoradiotherapy (nCRT) and surgery, which results in pathological complete response (pCR) in up to 30% of patients. Since epigenetic changes may influence response to therapy, we aimed to identify DNA methylation markers predictive of pCR in LARC patients treated with nCRT. We used high-throughput DNA methylation analysis of 32 treatment-naïve LARC biopsies and five normal rectal tissues to explore the predictive value of differentially methylated (DM) CpGs. External validation was carried out with The Cancer Genome Atlas-Rectal Adenocarcinoma (TCGA-READ 99 cases). A classifier based on three-CpGs DM (linked to OBSL1, GPR1, and INSIG1 genes) was able to discriminate pCR from incomplete responders with high sensitivity and specificity. The methylation levels of the selected CpGs confirmed the predictive value of our classifier in 77 LARCs evaluated by bisulfite pyrosequencing. Evaluation of external datasets (TCGA-READ, GSE81006, GSE75546, and GSE39958) reproduced our results. As the three CpGs were mapped near to regulatory elements, we performed an integrative analysis in regions associated with predicted cis-regulatory elements. A positive and inverse correlation between DNA methylation and gene expression was found in two CpGs. We propose a novel predictive tool based on three CpGs potentially useful for pretreatment screening of LARC patients and guide the selection of treatment modality.

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Epigenetics and Precision Oncology

Cited by 77 publications

References 66 publications

The potential role of leptin in tumor invasion and metastasis

The potential role of leptin in tumor invasion and metastasis

Epigenetics in Inflammatory Breast Cancer: Biological Features and Therapeutic Perspectives

Comprehensive Analysis of DNA Methylation and Prediction of Response to NeoadjuvantTherapy in Locally Advanced Rectal Cancer

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