Pancreatic cancer

Pancreatic cancer is a notoriously lethal condition characterised by aggressive malignancy and dismal outcomes. However, translational advances are showing us that hope is on the horizon.

The application of single-cell RNA sequencing platforms has generated notable insights into the heterogeneity underlying pancreatic ductal adenocarcinoma (PDAC), encompassing both the neoplastic compartment and the tumour microenvironment. In this Comment, we discuss the most pertinent findings gleaned from both mouse models and human PDAC samples, as well as future opportunities.

Pancreatic ductal adenocarcinoma (PDAC) reflects the current challenge for immuno-oncology: to develop new drugs for cancers that are resistant to current immunotherapies. Here, we argue for a need to use patients to uncover new strategies that activate anti-tumour immunity.

Vast developments are being made within the field of pancreatic cancer genomics. This Review discusses the wide-ranging and most current research with the goal of integrating this information into a unifying description of the life history of pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) has a unique tumour microenvironment. Notably, PDAC can reprogramme metabolism in response to this microenvironment. This Review discusses metabolism in pancreatic cancer, including insights into mechanisms and processes as well as the potential therapeutic applications.

Pancreatic cancer is a leading cause of cancer death worldwide. This Review outlines the current knowledge of established pancreatic cancer risk factors, including lifestyle and inherited risk factors.

Pancreatic cancer is typically diagnosed at a late stage and early detection is a priority. This Review focuses on precancerous lesions of the pancreas, describing their pathological and molecular features and highlighting different DNA-based molecular approaches for early detection and their clinical utility.

The application of single-cell RNA sequencing platforms has generated notable insights into the heterogeneity underlying pancreatic ductal adenocarcinoma (PDAC), encompassing both the neoplastic compartment and the tumour microenvironment. In this Comment, we discuss the most pertinent findings gleaned from both mouse models and human PDAC samples, as well as future opportunities.

In 2020, important advances were made across three major frontiers of pancreatic ductal adenocarcinoma (PDAC) research: risk factors, therapeutic resistance and tumour recurrence. Pathophysiology of obesity-mediated PDAC initiation was elucidated, novel stromal mechanisms of therapeutic resistance were unveiled and the genetic evolution of recurrent PDAC under therapeutic pressures was tracked in human samples.

Most patients who undergo curative intent surgery for pancreatic cancer will still die of recurrent disease. A new study shows that pancreatic tumours that pass through the genetic bottlenecks of surgery and additional chemoradiotherapy have altered mutational signatures, driver genes and subclonal architecture.

Obesity is a known risk factor for pancreatic cancer. Now, a new study reports that obesity accelerates early pancreatic cancer development and growth in mice through local perturbations in the pancreatic microenvironment and implicates pancreatic islet-derived cholecystokinin as a driving factor.

The neoplastic epithelium of pancreatic cancer exists within a dense stroma that is recognized as a critical mediator of disease progression. This Review discusses our current understanding of the three principal constituents of pancreatic cancer stroma, their effect on the prevalent immune landscape and promising therapeutic targets within this compartment.

KRAS mutations are identified in >80% of patients with pancreatic ductal adenocarcinoma and tend to be associated with reduced overall survival. This Review discusses the role of oncogenic KRAS in the biology, diagnosis, prognosis and treatment of pancreatic cancer.