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Gene expression divides pancreatic ductal adenocarcinoma into two main types: classical, the commoner, which keeps its pancreatic identity and responds better to chemotherapy, and basal-like or squamous, which has lost it and carries a worse outlook. One gene, GATA6, is high in classical and low in basal-like tumours, so it can stand in for the whole test; it is used in trials, not routine care.
Three classifications converged. Collisson (2011) combined expression profiles of primary tumours and cell lines and found classical, quasimesenchymal and exocrine-like subtypes with different outcomes and drug responses (Collisson 2011). Moffitt (2015) digitally separated tumour from stroma and defined two tumour subtypes, classical and a basal-like subtype with worse outcome that resembles basal tumours of the bladder and breast, plus normal and activated stromal subtypes that are independently prognostic (Moffitt 2015). Bailey (2016) analysed 456 genomes and transcriptomes and named four subtypes, squamous (enriched for TP53 and KDM6A mutations, a TP63 network and hypermethylation of pancreatic endodermal genes, with poor prognosis), pancreatic progenitor, immunogenic and aberrantly differentiated endocrine exocrine (ADEX) (Bailey 2016); the squamous and quasimesenchymal groups are the basal-like tumours, and the later exocrine-like, ADEX and immunogenic groups largely reflect contaminating normal or immune tissue. Purified epithelium showed the subtypes are a continuum produced by mixtures of tumour subpopulations, linked to copy-number changes in mutant KRAS and GATA6 that arise through tetraploidisation during progression (Chan-Seng-Yue 2020). Clinical weight: in the COMPASS trial, which sequenced fresh biopsies before first-line chemotherapy, 20 percent of 195 patients were basal-like and 80 percent classical; the objective response rate was 10 percent against 33 percent, 60 percent of basal-like patients progressed on modified FOLFIRINOX against 15 percent of classical, and median overall survival was 5.9 against 9.3 months (hazard ratio 0.47 for classical); GATA6 expression by RNA sequencing or in situ hybridisation tracked the classifier closely, and basal-like tumours could be marked by keratin 5, were more hypoxic and carried a T-cell-inflamed signature (Aung 2018; O'Kane 2020). What it means for a patient: the subtype is a research classification measured on biopsies in trials such as COMPASS and its successors, not a test the NHS reports; classical tumours are the ones in which the standard regimens do most, basal-like tumours are where new approaches are being sought, and GATA6 immunohistochemistry or in situ hybridisation is the candidate for a cheap routine surrogate. The parent record lists the subtypes as strings and the evidence layer carries the trials.
In plain words · KRAS is the most commonly mutated cancer gene, called 'undruggable' for 40 years until 2021.
Showing the target this term concerns: KRAS.
Shares Grade, Histopathology & immunohistochemistry, TP53, KRAS and the tags gi, pancreatic.
Shares Grade, Pancreatic cancer (KEGG map), Epithelial-mesenchymal transition & drug efflux, Gemcitabine + nab-paclitaxel and the tags gi, pancreatic.
Shares Gemcitabine + nab-paclitaxel, FOLFIRINOX / mFOLFIRINOX, Pancreatic ductal adenocarcinoma and the tags gi, pancreatic.
Shares Histopathology & immunohistochemistry, Resectable pancreatic ductal adenocarcinoma, Pancreatic ductal adenocarcinoma and the tags gi, pancreatic.
Shares Grade, Pancreatic cancer (KEGG map), Gemcitabine + nab-paclitaxel, FOLFIRINOX / mFOLFIRINOX and the tags gi, pancreatic.
Shares FOLFIRINOX / mFOLFIRINOX, Resectable pancreatic ductal adenocarcinoma, Pancreatic ductal adenocarcinoma and the tags gi, pancreatic.
Shares Metastatic pancreatic ductal adenocarcinoma, Pancreatic ductal adenocarcinoma and the tags gi, pancreatic.
Shares Resectable pancreatic ductal adenocarcinoma, Metastatic pancreatic ductal adenocarcinoma, Pancreatic ductal adenocarcinoma and the tags gi, pancreatic.