{"entity":{"id":"paper-heining-nrg1-fusions-kras-wild-type-pancreatic-cancer-discov-2018","kind":"paper","name":"Heining 2018: NRG1 fusions in KRAS wild-type pancreatic cancer","aka":[],"tldr":"Whole-genome and RNA sequencing of pancreatic cancers in younger patients found that most of the tumours without a KRAS mutation instead carried a fusion of the NRG1 gene, and two patients given a HER-family blocker responded. It established NRG1 fusions as the driver to look for in KRAS wild-type pancreatic cancer.","summary":"Report from the German NCT/DKTK MASTER precision oncology programme on whole-genome and transcriptome sequencing of pancreatic ductal adenocarcinomas from young patients (50 or under). Among the tumours without a KRAS mutation, most harboured an NRG1 gene fusion, whereas no KRAS-mutant tumour did.\n\nTwo patients with NRG1 fusion-positive tumours treated with the ERBB inhibitor afatinib had clinical and radiological responses, providing the first evidence that these fusions are actionable in pancreatic cancer and that RNA-level analysis is needed to find them.","asOf":"2026-09-21","links":[{"label":"Cancer Discov 2018","url":"https://doi.org/10.1158/2159-8290.CD-18-0036"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29802158/"}],"tags":[],"related":["kras-g12d"],"cancers":["kras-wild-type-pdac","pancreatic"],"sections":[],"technologies":["wes-wgs","rna-seq"],"targets":["nrg1","kras","her3"],"drugs":["afatinib"],"companies":[],"institutions":["dkfz","heidelberg-nct"],"pathways":["rtk-activation","ras-mapk"],"terms":["wild-type"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-discovery"],"dependsOn":[],"notes":[],"journal":"Cancer Discovery","year":2018,"doi":"10.1158/2159-8290.CD-18-0036","pmid":"29802158","authors":"Heining C, Horak P, Uhrig S, et al.","paperType":"translational","findings":["NRG1 fusions were found in most KRAS wild-type pancreatic cancers in a young-onset cohort and in none of the KRAS-mutant tumours.","Two patients with NRG1 fusion-positive tumours responded to afatinib."],"whatItMeans":"KRAS wild-type status should trigger fusion testing, ideally by RNA sequencing, because NRG1 fusions can be targeted by HER-family inhibitors and now by zenocutuzumab.","caveats":["A small, young-onset cohort; the frequency of NRG1 fusions in unselected KRAS wild-type disease is lower.","Afatinib responses were anecdotal and often short."],"changedPractice":true},"route":"/key-papers/paper-heining-nrg1-fusions-kras-wild-type-pancreatic-cancer-discov-2018/","neighbours":{"biomarker":[{"id":"kras-g12d","kind":"biomarker","name":"KRAS G12D (and other non-G12C KRAS mutations)","route":"/biomarkers/kras-g12d/"}],"cancer":[{"id":"kras-wild-type-pdac","kind":"cancer","name":"KRAS wild-type pancreatic ductal adenocarcinoma","route":"/cancers/kras-wild-type-pdac/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"}],"technology":[{"id":"rna-seq","kind":"technology","name":"RNA sequencing & expression profiling","route":"/technologies/rna-seq/"},{"id":"wes-wgs","kind":"technology","name":"Whole-exome & whole-genome sequencing","route":"/technologies/wes-wgs/"}],"target":[{"id":"her3","kind":"target","name":"HER3","route":"/targets/her3/"},{"id":"kras","kind":"target","name":"KRAS","route":"/targets/kras/"},{"id":"nrg1","kind":"target","name":"NRG1","route":"/targets/nrg1/"}],"drug":[{"id":"afatinib","kind":"drug","name":"Afatinib","route":"/drugs/afatinib/"},{"id":"zenocutuzumab","kind":"drug","name":"Zenocutuzumab","route":"/drugs/zenocutuzumab/"}],"institution":[{"id":"dkfz","kind":"institution","name":"German Cancer Research Center (DKFZ)","route":"/institutions/dkfz/"},{"id":"heidelberg-nct","kind":"institution","name":"Heidelberg University Hospital / NCT / DKFZ","route":"/institutions/heidelberg-nct/"}],"pathway":[{"id":"ras-mapk","kind":"pathway","name":"RAS / RAF / MEK / ERK (MAPK)","route":"/pathways/ras-mapk/"},{"id":"rtk-activation","kind":"pathway","name":"Receptor tyrosine kinase activation","route":"/pathways/rtk-activation/"}],"term":[{"id":"wild-type","kind":"term","name":"Wild-type (WT)","route":"/terms/wild-type/"}],"journal":[{"id":"cancer-discovery","kind":"journal","name":"Cancer Discovery","route":"/journals/cancer-discovery/"}]}}