{"entity":{"id":"paper-beltran-nepc-aurka-mycn-cancer-discov-2011","kind":"paper","name":"Molecular characterisation of neuroendocrine prostate cancer and identification of new drug targets","aka":[],"tldr":"Profiling the rare aggressive form of prostate cancer found two genes amplified together in four out of ten cases, and blocking one of them switched off the neuroendocrine programme.","summary":"Using next-generation RNA sequencing and oligonucleotide arrays, 7 neuroendocrine prostate cancers, 30 prostate adenocarcinomas and 5 benign prostate tissues were profiled, with validation on a larger cohort of 37 neuroendocrine cancers, 169 adenocarcinomas and 22 benign tissues using immunohistochemistry and fluorescence in situ hybridisation. Significant overexpression and gene amplification of AURKA and MYCN were found in 40% of neuroendocrine prostate cancers and 5% of adenocarcinomas, with evidence that they cooperate to induce a neuroendocrine phenotype in prostate cells. Neuroendocrine cancers, and MYCN-overexpressing adenocarcinomas, were dramatically sensitive to Aurora kinase inhibitor therapy in vitro and in vivo, with complete suppression of neuroendocrine marker expression after treatment.","asOf":"2026-09-25","links":[{"label":"Beltran et al., Cancer Discov 2011: molecular characterisation of neuroendocrine prostate cancer, with AURKA and MYCN co-amplification in 40%","url":"https://doi.org/10.1158/2159-8290.CD-11-0130"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22389870/"}],"tags":[],"related":[],"cancers":["prostate","prostate-nepc"],"sections":[],"technologies":["rna-seq","cytogenetics-fish","histopathology-ihc"],"targets":["aurka","mycn"],"drugs":[],"companies":[],"institutions":[],"pathways":["lineage-plasticity-neuroendocrine","myc","mitotic-spindle-checkpoint"],"terms":["histologic-transformation","gene-amplification","fish"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-discovery"],"dependsOn":[],"notes":[],"journal":"Cancer Discovery","year":2011,"doi":"10.1158/2159-8290.CD-11-0130","pmid":"22389870","authors":"Beltran H, Rickman DS, Park K, et al.","paperType":"basic","findings":["AURKA and MYCN overexpressed and amplified in 40% of neuroendocrine prostate cancers against 5% of adenocarcinomas.","The two genes cooperate to induce a neuroendocrine phenotype in prostate cells.","Aurora kinase inhibition suppressed neuroendocrine marker expression in models."],"whatItMeans":"It was the first evidence that neuroendocrine prostate cancer is a distinct molecular disease with its own candidate drug target, and it started the programme of Aurora kinase trials in this setting, which have since disappointed.","caveats":["Seven neuroendocrine cancers in the discovery set, which is very few.","Aurora kinase inhibitors have not shown the activity in men that the models predicted.","Forty per cent is enrichment within a rare phenotype, not a prostate-wide frequency."],"changedPractice":false},"route":"/key-papers/paper-beltran-nepc-aurka-mycn-cancer-discov-2011/","neighbours":{"cancer":[{"id":"prostate-nepc","kind":"cancer","name":"Neuroendocrine and small-cell prostate cancer","route":"/cancers/prostate-nepc/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"}],"technology":[{"id":"cytogenetics-fish","kind":"technology","name":"Cytogenetics and FISH","route":"/technologies/cytogenetics-fish/"},{"id":"histopathology-ihc","kind":"technology","name":"Histopathology & immunohistochemistry","route":"/technologies/histopathology-ihc/"},{"id":"rna-seq","kind":"technology","name":"RNA sequencing & expression profiling","route":"/technologies/rna-seq/"}],"target":[{"id":"aurka","kind":"target","name":"AURKA","route":"/targets/aurka/"},{"id":"mycn","kind":"target","name":"MYCN (N-myc)","route":"/targets/mycn/"}],"pathway":[{"id":"lineage-plasticity-neuroendocrine","kind":"pathway","name":"Lineage plasticity & neuroendocrine transformation","route":"/pathways/lineage-plasticity-neuroendocrine/"},{"id":"mitotic-spindle-checkpoint","kind":"pathway","name":"Mitosis & the spindle assembly checkpoint","route":"/pathways/mitotic-spindle-checkpoint/"},{"id":"myc","kind":"pathway","name":"MYC","route":"/pathways/myc/"}],"term":[{"id":"fish","kind":"term","name":"FISH / ISH (in situ hybridisation)","route":"/terms/fish/"},{"id":"gene-amplification","kind":"term","name":"Gene amplification and copy-number change","route":"/terms/gene-amplification/"},{"id":"histologic-transformation","kind":"term","name":"Histologic transformation","route":"/terms/histologic-transformation/"}],"journal":[{"id":"cancer-discovery","kind":"journal","name":"Cancer Discovery","route":"/journals/cancer-discovery/"}],"biomarker":[{"id":"nepc-transformation","kind":"biomarker","name":"Treatment-emergent neuroendocrine transformation (recognising it)","route":"/biomarkers/nepc-transformation/"}]}}