With 5-year survival rates remaining constant at 6% and rising incidences associated with an epidemic in obesity and metabolic syndrome, pancreatic ductal adenocarcinoma (PDAC) is on track to become the second most common cause of cancer-related deaths by 2030. The high mortality rate of PDAC stems primarily from the lack of early diagnosis and ineffective treatment for advanced tumors. During the past decade, the comprehensive atlas of genomic alterations, the prominence of specific pathways, the preclinical validation of such emerging targets, sophisticated preclinical model systems, and the molecular classification of PDAC into specific disease subtypes have all converged to illuminate drug discovery programs with clearer clinical path hypotheses. A deeper understanding of cancer cell biology, particularly altered cancer cell metabolism and impaired DNA repair processes, is providing novel therapeutic strategies that show strong preclinical activity. Elucidation of tumor biology principles, most notably a deeper understanding of the complexity of immune regulation in the tumor microenvironment, has provided an exciting framework to reawaken the immune system to attack PDAC cancer cells. While the long road of translation lies ahead, the path to meaningful clinical progress has never been clearer to improve PDAC patient survival.

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Genetics and biology of pancreatic ductal adenocarcinoma

A substantial body of evidence supports that the gut microbiota plays a pivotal role in the regulation of metabolic, endocrine and immune functions. In recent years, there has been growing recognition of the involvement of the gut microbiota in the modulation of multiple neurochemical pathways through the highly interconnected gut-brain axis. Although amazing scientific breakthroughs over the last few years have expanded our knowledge on the communication between microbes and their hosts, the underpinnings of microbiota-gut-brain crosstalk remain to be determined. Short-chain fatty acids (SCFAs), the main metabolites produced in the colon by bacterial fermentation of dietary fibers and resistant starch, are speculated to play a key role in neuro-immunoendocrine regulation. However, the underlying mechanisms through which SCFAs might influence brain physiology and behavior have not been fully elucidated. In this review, we outline the current knowledge about the involvement of SCFAs in microbiota-gut-brain interactions. We also highlight how the development of future treatments for central nervous system (CNS) disorders can take advantage of the intimate and mutual interactions of the gut microbiota with the brain by exploring the role of SCFAs in the regulation of neuro-immunoendocrine function.

/pdf/the-role-of-short-chain-fatty-acids-from-gut-microbiota-in-pfyjfu52jz.pdf

The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication

Hijacking the E3 Ubiquitin Ligase Cereblon to Efficiently Target BRD4

Tetraploidy, aneuploidy and cancer.

Role of transforming growth factor-β superfamily signaling pathways in human disease

Beneficial Metabolic Effects of a Probiotic via Butyrate-induced GLP-1 Hormone Secretion

Transforming Growth Factor-β/Smad3 Signaling Regulates Insulin Gene Transcription and Pancreatic Islet β-Cell Function

Transforming growth factor-β pathway: Role in pancreas development and pancreatic disease

Tumor formation via loss of a molecular motor protein.

https://www.cell.com/cell-reports/pdf/S2211-1247(14)00761-X.pdf

Ji-Hyeon Lee

Papers

Beneficial Metabolic Effects of a Probiotic via Butyrate-induced GLP-1 Hormone Secretion

Transforming Growth Factor-β/Smad3 Signaling Regulates Insulin Gene Transcription and Pancreatic Islet β-Cell Function

Transforming growth factor-β pathway: Role in pancreas development and pancreatic disease

Tumor formation via loss of a molecular motor protein.

Transformation resistance in a premature aging disorder identifies a tumor-protective function of BRD4.