Missing links — epigenetic regulators of the pancreatic cancer–associated inflammation

2021 ◽  
Vol 135 (10) ◽  
pp. 1289-1293
Author(s):  
Gregor Werba ◽  
Tamas A. Gonda
Keyword(s):  
Pancreatic Cancer ◽  
Noncoding Rna ◽  
Current Knowledge ◽  
Treatment Strategies ◽  
Therapeutic Interventions ◽  
Ductal Adenocarcinoma ◽  
Gastrointestinal Cancers ◽  
Novel Treatment ◽  
Epigenetic Regulator ◽  
Novel Treatment Strategies

Abstract Pancreatic ductal adenocarcinoma (PDAC) features a hostile tumor microenvironment (TME) that renders it remarkably resistant to most therapeutic interventions. Consequently, survival remains among the poorest compared with other gastrointestinal cancers. Concerted efforts are underway to decipher the complex PDAC TME, break down barriers to efficacious therapies and identify novel treatment strategies. In the recent Clinical Science, Li and colleagues identify the long noncoding RNA KLHDC7B-DT as a crucial epigenetic regulator of IL-6 transcription in PDAC and illustrate its potent influences on the pancreatic TME. In this commentary, we introduce epigenetics in pancreatic cancer and put the findings by Li et al. in context with current knowledge.

scholarly journals Immune Cell Modulation of the Extracellular Matrix Contributes to the Pathogenesis of Pancreatic Cancer

Biomolecules ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 901
Author(s):  
Ramiz S. Ahmad ◽  
Timothy D. Eubank ◽  
Slawomir Lukomski ◽  
Brian A. Boone
Keyword(s):  
Pancreatic Cancer ◽  
Extracellular Matrix ◽  
Immune Cells ◽  
Immune Cell ◽  
Treatment Strategies ◽  
Stellate Cells ◽  
Pancreatic Stellate Cells ◽  
Ductal Adenocarcinoma ◽  
Cellular Mechanisms ◽  
Novel Treatment Strategies

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with a five-year survival rate of only 9%. PDAC is characterized by a dense, fibrotic stroma composed of extracellular matrix (ECM) proteins. This desmoplastic stroma is a hallmark of PDAC, representing a significant physical barrier that is immunosuppressive and obstructs penetration of cytotoxic chemotherapy agents into the tumor microenvironment (TME). Additionally, dense ECM promotes hypoxia, making tumor cells refractive to radiation therapy and alters their metabolism, thereby supporting proliferation and survival. In this review, we outline the significant contribution of fibrosis to the pathogenesis of pancreatic cancer, with a focus on the cross talk between immune cells and pancreatic stellate cells that contribute to ECM deposition. We emphasize the cellular mechanisms by which neutrophils and macrophages, specifically, modulate the ECM in favor of PDAC-progression. Furthermore, we investigate how activated stellate cells and ECM influence immune cells and promote immunosuppression in PDAC. Finally, we summarize therapeutic strategies that target the stroma and hinder immune cell promotion of fibrogenesis, which have unfortunately led to mixed results. An enhanced understanding of the complex interactions between the pancreatic tumor ECM and immune cells may uncover novel treatment strategies that are desperately needed for this devastating disease.

scholarly journals Current Landscape: The Mechanism and Therapeutic Impact of Obesity for Breast Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Chongru Zhao ◽  
Weijie Hu ◽  
Yi Xu ◽  
Dawei Wang ◽  
Yichen Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Energy Homeostasis ◽  
Treatment Strategies ◽  
Therapeutic Interventions ◽  
Novel Treatment ◽  
Common Cancer ◽  
Prevalence Of Obesity ◽  
Novel Treatment Strategies ◽  
Underlying Mechanisms ◽  
The Impact

Obesity is defined as a chronic disease induced by an imbalance of energy homeostasis. Obesity is a widespread health problem with increasing prevalence worldwide. Breast cancer (BC) has already been the most common cancer and one of the leading causes of cancer death in women worldwide. Nowadays, the impact of the rising prevalence of obesity has been recognized as a nonnegligible issue for BC development, outcome, and management. Adipokines, insulin and insulin-like growth factor, sex hormone and the chronic inflammation state play critical roles in the vicious crosstalk between obesity and BC. Furthermore, obesity can affect the efficacy and side effects of multiple therapies such as surgery, radiotherapy, chemotherapy, endocrine therapy, immunotherapy and weight management of BC. In this review, we focus on the current landscape of the mechanisms of obesity in fueling BC and the impact of obesity on diverse therapeutic interventions. An in-depth exploration of the underlying mechanisms linking obesity and BC will improve the efficiency of the existing treatments and even provide novel treatment strategies for BC treatment.

scholarly journals Emerging Role of miR-345 and Its Effective Delivery as a Potential Therapeutic Candidate in Pancreatic Cancer and Other Cancers

Pharmaceutics ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 1987
Author(s):  
Nagabhishek Sirpu Natesh ◽  
Brianna M. White ◽  
Maia M. C. Bennett ◽  
Metin Uz ◽  
Rakhee Rathnam Kalari Kandy ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Critical Role ◽  
Tumor Development ◽  
Treatment Strategies ◽  
Underlying Mechanism ◽  
Therapeutic Interventions ◽  
Ductal Adenocarcinoma ◽  
Desmoplastic Reaction ◽  
Cancer Pathogenesis ◽  
Effective Delivery

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with high mortality, poor prognosis, and palliative treatments, due to the rapid upregulation of alternative compensatory pathways and desmoplastic reaction. miRNAs, small non-coding RNAs, have been recently identified as key players regulating cancer pathogenesis. Dysregulated miRNAs are associated with molecular pathways involved in tumor development, metastasis, and chemoresistance in PDAC, as well as other cancers. Targeted treatment strategies that alter miRNA levels in cancers have promising potential as therapeutic interventions. miRNA-345 (miR-345) plays a critical role in tumor suppression and is differentially expressed in various cancers, including pancreatic cancer (PC). The underlying mechanism(s) and delivery strategies of miR-345 have been investigated by us previously. Here, we summarize the potential therapeutic roles of miR-345 in different cancers, with emphasis on PDAC, for miRNA drug discovery, development, status, and implications. Further, we focus on miRNA nanodelivery system(s), based on different materials and nanoformulations, specifically for the delivery of miR-345.

scholarly journals The Evolving Understanding of the Molecular and Therapeutic Landscape of Pancreatic Ductal Adenocarcinoma

Diseases ◽  
2018 ◽  
Vol 6 (4) ◽  
pp. 103 ◽  
Author(s):  
Ashleigh Parkin ◽  
Jennifer Man ◽  
Angela Chou ◽  
Adnan Nagrial ◽  
Jaswinder Samra ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Treatment Strategies ◽  
Current Status ◽  
Ductal Adenocarcinoma ◽  
Molecular Heterogeneity ◽  
Precision Oncology ◽  
Molecular Stratification ◽  
Therapeutic Landscape ◽  
Genomic Fingerprint ◽  
Novel Treatment Strategies

Pancreatic cancer is the third leading cause of cancer-related deaths, characterised by poor survival, marked molecular heterogeneity and high intrinsic and acquired chemoresistance. Only 10–20% of pancreatic cancer patients present with surgically resectable disease and even then, 80% die within 5 years. Our increasing understanding of the genomic heterogeneity of cancer suggests that the failure of definitive clinical trials to demonstrate efficacy in the majority of cases is likely due to the low proportion of responsive molecular subtypes. As a consequence, novel treatment strategies to approach this disease are urgently needed. Significant developments in the field of precision oncology have led to increasing molecular stratification of cancers into subtypes, where individual cancers are selected for optimal therapy depending on their molecular or genomic fingerprint. This review provides an overview of the current status of clinically used and emerging treatment strategies, and discusses the advances in and the potential for the implementation of precision medicine in this highly lethal malignancy, for which there are currently no curative systemic therapies.

scholarly journals Methyladenosine Modification in RNAs: Classification and Roles in Gastrointestinal Cancers

2021 ◽  
Vol 10 ◽  
Author(s):  
Qinghai Li ◽  
Weiling He ◽  
Guohui Wan
Keyword(s):  
Molecular Mechanisms ◽  
Treatment Strategies ◽  
Messenger Rnas ◽  
Epigenetic Changes ◽  
Gastrointestinal Cancers ◽  
Ribonucleic Acids ◽  
Rna Methylation ◽  
Novel Treatment ◽  
Non Coding Rnas ◽  
Novel Treatment Strategies

Cellular ribonucleic acids (RNAs), including messenger RNAs (mRNAs) and non-coding RNAs (ncRNAs), harbor more than 150 forms of chemical modifications, among which methylation modifications are dynamically regulated and play significant roles in RNA metabolism. Recently, dysregulation of RNA methylation modifications is found to be linked to various physiological bioprocesses and many human diseases. Gastric cancer (GC) and colorectal cancer (CRC) are two main gastrointestinal-related cancers (GIC) and the most leading causes of cancer-related death worldwide. In-depth understanding of molecular mechanisms on GIC can provide important insights in developing novel treatment strategies for GICs. In this review, we focus on the multitude of epigenetic changes of RNA methlyadenosine modifications in gene expression, and their roles in GIC tumorigenesis, progression, and drug resistance, and aim to provide the potential therapeutic regimens for GICs.

Oncology Scan—Novel Treatment Strategies for Gastrointestinal Cancers

2014 ◽  
Vol 89 (4) ◽  
pp. 699-703 ◽  
Author(s):  
Daniel T. Chang ◽  
Thomas Brunner ◽  
Jason Chia-Hsien Cheng ◽  
Stanley Liauw ◽  
Jeffrey Meyer ◽  
...  
Keyword(s):  
Treatment Strategies ◽  
Gastrointestinal Cancers ◽  
Novel Treatment ◽  
Novel Treatment Strategies

scholarly journals Current Insights into Immunology and Novel Therapeutics of Atopic Dermatitis

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1392
Author(s):  
Hidaya A. Kader ◽  
Muhammad Azeem ◽  
Suhib A. Jwayed ◽  
Aaesha Al-Shehhi ◽  
Attia Tabassum ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Skin Diseases ◽  
Current Knowledge ◽  
Treatment Strategies ◽  
Developed Countries ◽  
Food Allergies ◽  
Th2 Response ◽  
Therapeutic Outcomes ◽  
Environmental Agents ◽  
Novel Treatment Strategies

Atopic dermatitis (AD) is one of the most prevalent inflammatory disease among non-fatal skin diseases, affecting up to one fifth of the population in developed countries. AD is characterized by recurrent pruritic and localized eczema with seasonal fluctuations. AD initializes the phenomenon of atopic march, during which infant AD patients are predisposed to progressive secondary allergies such as allergic rhinitis, asthma, and food allergies. The pathophysiology of AD is complex; onset of the disease is caused by several factors, including strong genetic predisposition, disrupted epidermal barrier, and immune dysregulation. AD was initially characterized by defects in the innate immune system and a vigorous skewed adaptive Th2 response to environmental agents; there are compelling evidences that the disorder involves multiple immune pathways. Symptomatic palliative treatment is the only strategy to manage the disease and restore skin integrity. Researchers are trying to more precisely define the contribution of different AD genotypes and elucidate the role of various immune axes. In this review, we have summarized the current knowledge about the roles of innate and adaptive immune responsive cells in AD. In addition, current and novel treatment strategies for the management of AD are comprehensively described, including some ongoing clinical trials and promising therapeutic agents. This information will provide an asset towards identifying personalized targets for better therapeutic outcomes.

scholarly journals Unique Genomic Landscape of High-Grade Neuroendocrine Cervical Carcinoma: Implications for Rethinking Current Treatment Paradigms

2020 ◽  
pp. 972-987
Author(s):  
Ramez N. Eskander ◽  
Julia Elvin ◽  
Laurie Gay ◽  
Jeffrey S. Ross ◽  
Vincent A. Miller ◽  
...  
Keyword(s):  
Treatment Strategies ◽  
Current Treatment ◽  
High Grade ◽  
Novel Treatment ◽  
Sample Average ◽  
Genomic Landscape ◽  
Comprehensive Genomic Profiling ◽  
Tumor Mutational Burden ◽  
Sample Range ◽  
Novel Treatment Strategies

PURPOSE High-grade neuroendocrine cervical cancer (HGNECC) is an uncommon malignancy with limited therapeutic options; treatment is patterned after the histologically similar small-cell lung cancer (SCLC). To better understand HGNECC biology, we report its genomic landscape. PATIENTS AND METHODS Ninety-seven patients with HGNECC underwent comprehensive genomic profiling (182-315 genes). These results were subsequently compared with a cohort of 1,800 SCLCs. RESULTS The median age of patients with HGNECC was 40.5 years; 83 patients (85.6%) harbored high-risk human papillomavirus (HPV). Overall, 294 genomic alterations (GAs) were identified (median, 2 GAs/sample; average, 3.0 GAs/sample, range, 0-25 GAs/sample) in 109 distinct genes. The most frequently altered genes were PIK3CA (19.6% of cohort), MYC (15.5%), TP53 (15.5%), and PTEN (14.4%). RB1 GAs occurred in 4% versus 32% of HPV-positive versus HPV-negative tumors ( P < .0001). GAs in HGNECC involved the following pathways: PI3K/AKT/mTOR (41.2%); RAS/MEK (11.3%); homologous recombination (9.3%); and ERBB (7.2%). Two tumors (2.1%) had high tumor mutational burden (TMB; both with MSH2 alterations); 16 (16.5%) had intermediate TMB. Seventy-one patients (73%) had ≥ 1 alteration that was theoretically druggable. Comparing HGNECC with SCLC, significant differences in TMB, microsatellite instability, HPV-positive status, and in PIK3CA, MYC, PTEN, TP53, ARID1A, and RB1 alteration rates were found. CONCLUSION This large cohort of patients with HGNECC demonstrated a genomic landscape distinct from SCLC, calling into question the biologic and therapeutic relevance of the histologic similarities between the entities. Furthermore, 73% of HGNECC tumors had potentially actionable alterations, suggesting novel treatment strategies for this aggressive malignancy.

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