{"entity":{"id":"paper-bluemn-double-negative-prostate-fgf-mapk-cancer-cell-2017","kind":"paper","name":"Androgen receptor pathway-independent prostate cancer is sustained through FGF signalling","aka":[],"tldr":"Over two decades a new kind of advanced prostate cancer appeared that uses neither the androgen receptor nor a neuroendocrine programme, and it runs on a growth factor pathway instead.","summary":"Androgen receptor signalling is the distinctive feature of prostate carcinoma and the major therapeutic target in metastatic disease, but androgen receptor antagonism can produce tumours that bypass a functional requirement for the receptor, often through neuroendocrine transdifferentiation. Through molecular assessment of metastatic prostate cancers over two decades, a phenotypic shift was found with the emergence of an androgen receptor-null, neuroendocrine-null phenotype. These double-negative prostate cancers showed elevated FGF and MAPK pathway activity, which can bypass androgen receptor dependence, and pharmacological inhibitors of MAPK or FGFR repressed their growth in vitro and in vivo.","asOf":"2026-09-25","links":[{"label":"Bluemn et al., Cancer Cell 2017: androgen receptor pathway-independent, neuroendocrine-null metastatic prostate cancer sustained by FGF and MAPK signalling","url":"https://doi.org/10.1016/j.ccell.2017.09.003"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29017058/"}],"tags":[],"related":[],"cancers":["prostate","prostate-mcrpc","prostate-nepc"],"sections":[],"technologies":[],"targets":["androgen-receptor","fgfr1","mek"],"drugs":[],"companies":[],"institutions":[],"pathways":["ar-signaling","fgfr-signalling","ras-mapk","lineage-plasticity-neuroendocrine","resistance-routes-map"],"terms":["resistance","castration-resistance","histologic-transformation"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["cancer-cell"],"dependsOn":[],"notes":[],"journal":"Cancer Cell","year":2017,"doi":"10.1016/j.ccell.2017.09.003","pmid":"29017058","authors":"Bluemn EG, Coleman IM, Lucas JM, et al.","paperType":"basic","findings":["An androgen receptor-null, neuroendocrine-null phenotype has emerged in metastatic prostate cancer over two decades.","Double-negative tumours show elevated FGF and MAPK pathway activity.","MAPK or FGFR inhibition repressed growth of these tumours in vitro and in vivo."],"whatItMeans":"It shows that leaving androgen receptor dependence does not have to mean becoming neuroendocrine, and it names a treatable pathway for a group of men whose tumours would otherwise be described only by what they lack.","caveats":["A research autopsy and xenograft series rather than a prospective clinical cohort.","The phenotypic shift over time is inferred from samples collected under changing treatment practice.","No FGFR or MEK inhibitor is approved in prostate cancer."],"changedPractice":false},"route":"/key-papers/paper-bluemn-double-negative-prostate-fgf-mapk-cancer-cell-2017/","neighbours":{"cancer":[{"id":"prostate-mcrpc","kind":"cancer","name":"Metastatic castration-resistant prostate cancer","route":"/cancers/prostate-mcrpc/"},{"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/"}],"target":[{"id":"androgen-receptor","kind":"target","name":"Androgen receptor","route":"/targets/androgen-receptor/"},{"id":"fgfr1","kind":"target","name":"FGFR1","route":"/targets/fgfr1/"},{"id":"mek","kind":"target","name":"MEK1/2","route":"/targets/mek/"}],"pathway":[{"id":"ar-signaling","kind":"pathway","name":"Androgen receptor signalling","route":"/pathways/ar-signaling/"},{"id":"fgfr-signalling","kind":"pathway","name":"FGF / FGFR signalling","route":"/pathways/fgfr-signalling/"},{"id":"lineage-plasticity-neuroendocrine","kind":"pathway","name":"Lineage plasticity & neuroendocrine transformation","route":"/pathways/lineage-plasticity-neuroendocrine/"},{"id":"ras-mapk","kind":"pathway","name":"RAS / RAF / MEK / ERK (MAPK)","route":"/pathways/ras-mapk/"},{"id":"resistance-routes-map","kind":"pathway","name":"Resistance routes: how a blocked pathway comes back","route":"/pathways/resistance-routes-map/"}],"term":[{"id":"castration-resistance","kind":"term","name":"Castration-resistant prostate cancer (CRPC)","route":"/terms/castration-resistance/"},{"id":"resistance","kind":"term","name":"Drug resistance (primary and acquired)","route":"/terms/resistance/"},{"id":"histologic-transformation","kind":"term","name":"Histologic transformation","route":"/terms/histologic-transformation/"}],"journal":[{"id":"cancer-cell","kind":"journal","name":"Cancer Cell","route":"/journals/cancer-cell/"}]}}