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Cancer cells often have extra copies of a growth gene (amplification) or have lost copies of a protective one (deletion), rather than a spelling change within the gene. Extra copies of HER2 or MYCN are classic examples that change treatment.
Amplification (detected by FISH, ISH or NGS copy-number calls) drives overexpression: HER2 in breast and gastric cancer, MYCN in high-risk neuroblastoma, MET amplification as a resistance route to EGFR inhibitors, CCNE1 in ovarian and gastric cancer, MDM2 in liposarcoma, CDK4 in glioma. Deletions remove tumour suppressors: del(17p)/TP53 in CLL and myeloma (predicting chemo-resistance), CDKN2A/B in glioma (defining grade 4), MTAP (creating a PRMT5 vulnerability), 9p21 loss linked to immunotherapy resistance. Loss of heterozygosity and large-scale copy changes are summed into genomic-scar scores used to infer HRD and predict PARP inhibitor benefit.
In plain words · A growth-signal receptor. Some cancers make far too much of it, and drugs that block it or use it as a docking site have transformed those cancers.
Showing the target this term concerns: HER2.
The glossary entry explains the word; the readout page carries the scoring rule, the thresholds approvals use, the companion diagnostics and the tests.
This is the paper Europe PMC returns for registry id NCT04744831 with the most citations, so it is the natural first reading for anyone following the DESTINY-CRC02 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.
The first United States approval of a HER2-directed regimen in colorectal cancer, and the basis for MOUNTAINEER-03, which is testing the combination with chemotherapy in the first line.
It is the proof that plasma genotyping can enrol patients for a targeted colorectal trial, which matters most for a 2 to 3% alteration where archival tissue is often exhausted or out of date.
It shows that the commonest driver event in advanced prostate cancer is invisible to the panels used to test for it, and that the shape of the structural damage in a genome tells you which repair pathway failed, which is information a mutation list does not carry.
It made MET exon 14 a clinical entity rather than a sequencing curiosity, and identified the patients most likely to be missed: older people whose age would otherwise argue against broad sequencing.
It is the threshold behind the colorectal HER2 approvals: the more-than-50% rule, rather than the 10% used in gastric cancer, is what a pathologist applies when a bowel cancer is called HER2-positive.
It explained why squamous lung cancer has no equivalent of an EGFR inhibitor: its commonest alterations are a transcription factor amplicon, a tumour suppressor deletion and an antioxidant switch, none of which is a drug target in the way a mutant kinase is.
It is where HER2-directed colorectal therapy came from: the xenopatient result led directly to HERACLES and therefore to every HER2 regimen now used in the disease.
Shares Trastuzumab deruxtecan in patients with HER2-positive advanced colorectal cancer (DESTINY-CRC02): primary results from a multicentre, randomised, phase 2 trial, Assessment of a HER2 scoring system for colorectal cancer: results from a validation study, Tucatinib plus trastuzumab for chemotherapy-refractory, HER2-positive, RAS wild-type unresectable or metastatic colorectal cancer (MOUNTAINEER), HER2 testing in biliary tract cancer (IHC, ISH and NGS).
Shares HER2 testing in biliary tract cancer (IHC, ISH and NGS), HER2 ISH amplified (ERBB2 gene amplification), HER2-positive (IHC 3+ or ISH-amplified), FISH / ISH (in situ hybridisation).
Shares HER2 testing in biliary tract cancer (IHC, ISH and NGS), HER2 ISH amplified (ERBB2 gene amplification), HER2-positive (IHC 3+ or ISH-amplified), FISH / ISH (in situ hybridisation).
Shares Frequent and focal FGFR1 amplification associates with therapeutically tractable FGFR1 dependency in squamous cell lung cancer, Molecular characterisation of neuroendocrine prostate cancer and identification of new drug targets, 9p24.1 alteration of the PD-1 ligand loci, In vivo amplification of the androgen receptor gene and progression of human prostate cancer.
Shares HER2 testing in biliary tract cancer (IHC, ISH and NGS), HER2 ISH amplified (ERBB2 gene amplification), HER2-positive (IHC 3+ or ISH-amplified), FISH / ISH (in situ hybridisation).
Shares MYCN (N-myc), Molecular characterisation of neuroendocrine prostate cancer and identification of new drug targets, AR amplification (gene and upstream enhancer), Histopathology & immunohistochemistry.
Shares Genomic hallmarks and structural variation in metastatic prostate cancer, AR amplification (gene and upstream enhancer), Comprehensive genomic characterization of squamous cell lung cancers, Prostate cancer.
Shares Trastuzumab deruxtecan in patients with HER2-positive advanced colorectal cancer (DESTINY-CRC02): primary results from a multicentre, randomised, phase 2 trial, Assessment of a HER2 scoring system for colorectal cancer: results from a validation study, HER2, Colorectal cancer.