Dr. Garyfalia Karponi
The event
On December 4, the U.S. Food and Drug Administration (FDA) granted accelerated approval to zenocutuzumab (Bizengri®) for use in patients with advanced pancreatic cancer or non-small cell lung cancer (NSCLC) harboring rearrangements (fusions) in the NRG1 gene, whose disease progressed after other treatments.
What are rearrangements (fusions)?
Rearrangements represent a category of alterations in genetic material that are attractive both as therapeutic targets and as diagnostic tools, due to their inherent expression exclusively in cancer tissues. In several cancers, rearrangements of specific genes are already pharmacologically targetable, while many of them are found in more than one type of cancer and are therefore characterized as tumor-agnostic.
How common are rearrangements in the NRG1 gene in NSCLC and pancreatic cancer?
Rearrangements in the NRG1 gene are rare. They are found in 0.2% of patients with NSCLC and pancreatic cancer. However, identifying such an alteration implies pharmacological targeting, offering to the patient a significant window of survival.
What we offer
Rearrangements involving the NRG1 gene are tested in our “C.A.RE. – Clinically Actionable REarrangements” test, where 49 driver genes are examined for possible rearrangements by NGS — see table below. This test can serve as a standalone package for any solid cancer, including NSCLC and pancreatic cancer.
| AKT1 | ERBB4 (HER4) | MET | NTRK3 | RET |
| AKT2 | ERG | MTAP | NUTM1 | ROS1 |
| AKT3 | ESR1 | MYB | PIK3CA | RSPO2 |
| ALK | ETV1 | MYBL1 | PIK3CB | RSPO3 |
| AR | ETV4 | NOTCH1 | PPARG | STAT6 |
| BRAF | ETV5 | NOTCH2 | PRKACA | TERT |
| BRCA1 | FGFR1 | NOTCH3 | PRKACB | TFE3 |
| CDKN2A | FGFR2 | NRG1 | RAF1 | TFEB |
| EGFR | FGFR3 | NTRK1 | RARA | YAP1 |
| ERBB2 (HER2) | MAP3K8 | NTRK2 | RELA |
Specifically for pancreatic cancer, the NRG1 gene is also tested for rearrangements in the “SomArray Pancreas Broad” package, which includes the following biomarkers:
- TMB, together with testing of 409 genes
- BRCA1, BRCA2
- HER2
- PD-L1
- MSI or MMR — MLH1, MSH2, MSH6, PMS2
- Testing for C.A.RE. rearrangements, as listed in the table above
How can I take the test?
Molecular testing is performed on tissue or cell specimens from the affected site, obtained through biopsy or surgical excision. These are usually fixed in the pathology laboratory and embedded in the commonly referred “paraffin blocks.”
Please contact us for more information.
Garyfalia Karponi, MSc, PhD
Molecular Biologist-Geneticist
Chief Scientific Officer, Department of Molecular Diagnostics