# Heining 2018: NRG1 fusions in KRAS wild-type pancreatic cancer

Source: https://onco.cc/key-papers/paper-heining-nrg1-fusions-kras-wild-type-pancreatic-cancer-discov-2018/  
OnCo record `paper-heining-nrg1-fusions-kras-wild-type-pancreatic-cancer-discov-2018` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

Two 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.

## Fields

- Kind: Key paper
- Last checked: 2026-09-21
- Journal: Cancer Discovery
- Year: 2018
- DOI: 10.1158/2159-8290.CD-18-0036
- Authors: Heining C, Horak P, Uhrig S, et al.
- 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.
- What it means: 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.

## Sources

- Cancer Discov 2018: https://doi.org/10.1158/2159-8290.CD-18-0036
- PubMed: https://pubmed.ncbi.nlm.nih.gov/29802158/

## Connected records

- cancers: [KRAS wild-type pancreatic ductal adenocarcinoma](https://onco.cc/cancers/kras-wild-type-pdac/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/)
- drugs: [Afatinib](https://onco.cc/drugs/afatinib/)
- journals: [Cancer Discovery](https://onco.cc/journals/cancer-discovery/)

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