Organoid-based precision medicine in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) ranks among the leading causes of cancer-related deaths worldwide. Despite advances in precision oncology in other malignancies, treatment of PDAC still largely relies on conventional chemotherapy. Given the dismal prognosis and heterogeneity in PDAC, there is an urgent need for personalized therapeutic strategies to improve treatment response.

Barriers and opportunities for gemcitabine in pancreatic cancer therapy.

Pancreatic ductal adenocarcinoma (PDA) has become one of the leading causes of cancer-related deaths across the world. A lack of durable responses to standard-of-care chemotherapies renders its treatment particularly challenging and largely contributes to the devastating outcome. Gemcitabine, a pyrimidine antimetabolite, is a cornerstone in PDA treatment.

Differential integrated stress response and asparagine production drive symbiosis and therapy resistance of pancreatic adenocarcinoma cells.

The pancreatic tumor microenvironment drives deregulated nutrient availability. Accordingly, pancreatic cancer cells require metabolic adaptations to survive and proliferate. Pancreatic cancer subtypes have been characterized by transcriptional and functional differences, with subtypes reported to exist within the same tumor.

Targeting DNA Damage Repair Mechanisms in Pancreas Cancer.

Impaired DNA damage repair (DDR) is increasingly recognised as a hallmark in pancreatic ductal adenocarcinoma (PDAC). It is estimated that around 14% of human PDACs harbour mutations in genes involved in DDR, including, amongst others, , , , , and . Recently, DDR intervention by PARP inhibitor therapy has demonstrated effectiveness in germline -mutated PDAC.

Cabozantinib in Advanced Hepatocellular Carcinoma: Efficacy and Safety Data from an International Multicenter Real-Life Cohort.

Background And Aims: The multikinase inhibitor cabozantinib has been approved for hepatocellular carcinoma (HCC) previously treated with sorafenib. We report safety and efficacy data of an international, multicenter, real-life cohort of patients with advanced HCC treated with cabozantinib.

Methods: Patients with HCC who were treated with cabozantinib were retrospectively identified across 11 centers in Austria, Switzerland, and Germany.

Functional Genomic Screening During Somatic Cell Reprogramming Identifies DKK3 as a Roadblock of Organ Regeneration.

Somatic cell reprogramming and tissue repair share relevant factors and molecular programs. Here, Dickkopf-3 (DKK3) is identified as novel factor for organ regeneration using combined transcription-factor-induced reprogramming and RNA-interference techniques. Loss of enhances the generation of induced pluripotent stem cells but does not affect de novo derivation of embryonic stem cells, three-germ-layer differentiation or colony formation capacity of liver and pancreatic organoids.

A Prospective Feasibility Trial to Challenge Patient-Derived Pancreatic Cancer Organoids in Predicting Treatment Response.

Real-time isolation, propagation, and pharmacotyping of patient-derived pancreatic cancer organoids (PDOs) may enable treatment response prediction and personalization of pancreatic cancer (PC) therapy. In our methodology, PDOs are isolated from 54 patients with suspected or confirmed PC in the framework of a prospective feasibility trial. The drug response of single agents is determined by a viability assay.

Maintenance Therapy for ATM-Deficient Pancreatic Cancer by Multiple DNA Damage Response Interferences after Platinum-Based Chemotherapy.

Personalized medicine in treating pancreatic ductal adenocarcinoma (PDAC) is still in its infancy, albeit PDAC-related deaths are projected to rise over the next decade. Only recently, maintenance therapy with the PARP inhibitor olaparib showed improved progression-free survival in germline -mutated PDAC patients after platinum-based induction for the first time. Transferability of such a concept to other DNA damage response (DDR) genes remains unclear.

Pancreatic cancer-derived organoids - a disease modeling tool to predict drug response.

Background: Organotypic cultures derived from pancreatic ductal adenocarcinoma (PDAC) termed pancreatic ductal cancer organoids (PDOs) recapitulate the primary cancer and can be derived from primary or metastatic biopsies. Although isolation and culture of patient-derived pancreatic organoids were established several years ago, pros and cons for individualized medicine have not been comprehensively investigated to date.

Methods: We conducted a feasibility study, systematically comparing head-to-head patient-derived xenograft tumor (PDX) and PDX-derived organoids by rigorous immunohistochemical and molecular characterization.

Immunotherapy: Pancreatic Cancer and Extrahepatic Biliary Tract Cancer.

Pancreatic ductal adenocarcinoma (PDAC) and extrahepatic biliary tract cancer (BTC) are among the malignancies with the highest morbidity and mortality. Despite increasing knowledge on biology and novel therapies, outcome remains poor in these patients. Recent progress in immunotherapies created new hopes in the treatment of PDAC and extrahepatic BTC.

A Blood-Based Multi Marker Assay Supports the Differential Diagnosis of Early-Stage Pancreatic Cancer.

The most frequent malignancy of the pancreas is the pancreatic ductal adenocarcinoma (PDAC). Despite many efforts PDAC has still a dismal prognosis. Biomarkers for early disease stage diagnosis as a prerequisite for a potentially curative treatment are still missing.

Parameters of blood viscosity do not correlate with the extent of coronary and carotid atherosclerosis and with endothelial function in patients undergoing coronary angiography.

While the role of physical forces on the control of atherogenesis and the modulation of endothelial function is well known, studies investigating the impact of shear stress on the extent of central atherosclerosis and flow-mediated dilation in humans produced controversial results. We investigated the relationship between viscosity, coronary atherosclerosis, carotid intima-media thickness and flow-mediated dilation in patients undergoing coronary angiography. 451 patients (306 males, mean age 66 ± 10) were enrolled.

Evidence of a weak correlation between peripheral endothelial function measures and carotid intima-media thickness.

Previous studies from our and other laboratories have demonstrated the existence of a clear relationship between different measures of endothelial function and the extent of coronary atherosclerosis. The relationship between endothelial function and carotid intima-media thickness has not been extensively investigated. Endothelial function using radial artery flow-mediated constriction (L-FMC) and dilation (FMD) was assessed in 513 consecutive patients undergoing diagnostic coronary angiography.