A tangled tale of molecular subtypes in pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) constitutes the most common malignancy of the pancreas. With a 5-year survival rate of below 10% and a median survival of less than 12 months following diagnosis, PDAC remains a major biomedical challenge. Due to the lack of early symptoms patients are usually diagnosed with locally advanced or metastatic disease where surgical removal of the tumour is no longer feasible. Despite some recent developments in medical oncology, response to chemotherapeutic regimens such as nab-paclitaxel and FOLFIRINOX is limited and accompanied by side effects such as nausea, neutropenia, neuropathy and infectious complications.1 Histologically, the majority of PDAC cases are characterised by tubular adenocarcinoma of the ductal glands embedded in a pronounced tumour microenvironment (TME) composed of acellular components such as collagen, hyaluronic acid, fibronectin and abundant matricellular proteins. Moreover, inflammatory cells such as tumour-associated macrophages, tumour-associated neutrophils, regulatory T cells, cancer-associated fibroblasts and neural cells accumulate around neoplastic cells and actively contribute to TME formation and tumour-stroma crosstalk.2 Notably, histopathological features of PDAC have not yet been used to select therapeutic strategies. However, increasing evidence from other tumour entities such as breast, melanoma, lung or colon cancer suggest that molecular characteristics can vastly differ in microscopically indistinguishable cancers. With the advent of high-throughput sequencing technologies such as whole-genome profiling and transcriptome profiling, molecular taxonomy of cancers has become …