Zakari, SuleimanRotimi, Solomon O.Bholah, Chandra TatshaOgunlana, OlubankeO.2026-02-092025https://doi.org/10.1155/sci5/4084224https://repository.covenantuniversity.edu.ng/handle/123456789/50594Speckle-type poxvirusandzinc*ngerprotein(SPOP)hasemergedasakeyfocusinprostatecancerresearchduetoitscriticalrole in regulatingtheandrogenreceptor(AR)signalingpathway./isreviewaimstocomprehensivelysummarizecurrentknowledge on SPOPgenemutationsinprostatecancer,emphasizingtheirimportanceindiseasecharacterizationandidenti*cationof therapeutic targets.Asystematicliteraturesearchwasconductedacrossmultipledatabases,includingPubMed,WebofScience, Scopus, andGoogleScholar.Inaddition,thisstudyusescomputationalapproachesanddatafromtheTCGAcBioPortaldatabase to explorethelandscapeofSPOPmutationsinprostatecancer.Afterscreening682articlesandfollowingsystematicselection steps, 56high-qualityarticleswereincluded.ComputationalanalysisofTCGAcBioPortaldatarevealedaSPOPmutation prevalence of5%-6%,alongwithsigni*cantalterationsinARsignalingandepigeneticregulation.SPOPmutationsdisrupt substrate recognition,leadingtodysregulationofdownstreampathwayssuchasARsignalingandchromatinremodeling. Notably, SPOP-mutantprostatecancersaremutuallyexclusivewithTMPRSS2-ERGfusionsandenrichedforWntpathway alterations. PatientswithSPOPmutationsdemonstrateprolongedresponsestoandrogendeprivationtherapy(ADT),although concurrent mutationsinTP53orDNArepairgenesnegativelyimpactoutcomes.Whiletheirprognosticsigni*cancecontinuesto evolve, theirimpactontheARpathwayhighlightstheirpotentialastherapeutictargets./eclinicalimplicationsofSPOP mutations aresubstantial,astheyarelinkedtovariationsintreatmentresponseanddiseaseprogression,thusservingasvaluable biomarkers forriskstrati*cationandprognosis.enandrogen receptorprostatecancerSPOPgeneSPOPmutationsTCGAcBioPortaltherapeutictargetsArticle