Autophagy as a critical driver of metabolic adaptation, therapeutic resistance, and immune evasion of cancer.

Autophagy is a well-conserved intracellular degradation pathway. Besides its physiological role in normal cells, autophagy is activated in various cancer types and protects cancer cells from stresses such as nutrient deprivation, therapeutic insults, and antitumor immunity. Autophagy in cancer cells as well as normal cells in the host supports tumor metabolism, allowing for tumor growth under a nutrient-limited tumor microenvironment.

HNF1B-driven three-dimensional chromatin structure for molecular classification in pancreatic cancers.

The molecular subtypes of pancreatic cancer (PC), either classical/progenitor-like or basal/squamous-like, are currently a major topic of research because of their direct association with clinical outcomes. Some transcription factors (TFs) have been reported to be associated with these subtypes. However, the mechanisms by which these molecular signatures of PCs are established remain unknown.

Targeting the Metabolic Rewiring in Pancreatic Cancer and Its Tumor Microenvironment.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with only a few effective therapeutic options. A characteristic feature of PDAC is its unique tumor microenvironment (TME), termed desmoplasia, which shows extensive fibrosis and extracellular matrix deposition, generating highly hypoxic and nutrient-deprived conditions within the tumor. To thrive in this harsh TME, PDAC undergoes extensive metabolic rewiring that includes the altered use of glucose and glutamine, constitutive activation of autophagy-lysosomal pathways, and nutrient acquisition from host cells in the TME.

Targeting autophagy as a therapeutic strategy against pancreatic cancer.

Macroautophagy (hereafter autophagy) is a catabolic process through which cytosolic components are captured in the autophagosome and degraded in the lysosome. Autophagy plays two major roles: nutrient recycling under starvation or stress conditions and maintenance of cellular homeostasis by removing the damaged organelles or protein aggregates. In established cancer cells, autophagy-mediated nutrient recycling promotes tumor progression, whereas in normal/premalignant cells, autophagy suppresses tumor initiation by eliminating the oncogenic/harmful molecules.

MNX1-HNF1B Axis Is Indispensable for Intraductal Papillary Mucinous Neoplasm Lineages.

Background & Aims: Chromatin architecture governs cell lineages by regulating the specific gene expression; however, its role in the diversity of cancer development remains unknown. Among pancreatic cancers, pancreatic ductal adenocarcinoma (PDAC) and intraductal papillary mucinous neoplasms (IPMN) with an associated invasive carcinoma (IPMNinv) arise from 2 distinct precursors, and their fundamental differences remain obscure. Here, we aimed to assess the difference of chromatin architecture regulating the transcriptional signatures or biological features in pancreatic cancers.

The Long-term Outcomes after VAD plus SCT Therapy in a Patient with AL Amyloidosis and Severe Factor X Deficiency.

A 55-year-old man was admitted to our institute to undergo evaluation for proteinuria (5.4 g/day) with lambda-type Bence-Jones protein (BJP). Primary amyloid light chain (AL) amyloidosis and acquired factor X deficiency were diagnosed.