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Exploring anti-androgen therapies in hormone dependent prostate cancer and new therapeutic routes for castration resistant prostate cancer.
Harris, Anna E; Metzler, Veronika M; Lothion-Roy, Jennifer; Varun, Dhruvika; Woodcock, Corinne L; Haigh, Daisy B; Endeley, Chantelle; Haque, Maria; Toss, Michael S; Alsaleem, Mansour; Persson, Jenny L; Gudas, Lorraine J; Rakha, Emad; Robinson, Brian D; Khani, Francesca; Martin, Laura M; Moyer, Jenna E; Brownlie, Juliette; Madhusudan, Srinivasan; Allegrucci, Cinzia; James, Victoria H; Rutland, Catrin S; Fray, Rupert G; Ntekim, Atara; de Brot, Simone; Mongan, Nigel P; Jeyapalan, Jennie N.
Afiliación
  • Harris AE; University of Nottingham Biodiscovery Institute, University of Nottingham, University Park, Nottingham, United Kingdom.
  • Metzler VM; University of Nottingham Biodiscovery Institute, University of Nottingham, University Park, Nottingham, United Kingdom.
  • Lothion-Roy J; University of Nottingham Biodiscovery Institute, University of Nottingham, University Park, Nottingham, United Kingdom.
  • Varun D; University of Nottingham Biodiscovery Institute, University of Nottingham, University Park, Nottingham, United Kingdom.
  • Woodcock CL; University of Nottingham Biodiscovery Institute, University of Nottingham, University Park, Nottingham, United Kingdom.
  • Haigh DB; University of Nottingham Biodiscovery Institute, University of Nottingham, University Park, Nottingham, United Kingdom.
  • Endeley C; University of Nottingham Biodiscovery Institute, University of Nottingham, University Park, Nottingham, United Kingdom.
  • Haque M; University of Nottingham Biodiscovery Institute, University of Nottingham, University Park, Nottingham, United Kingdom.
  • Toss MS; University of Nottingham Biodiscovery Institute, University of Nottingham, University Park, Nottingham, United Kingdom.
  • Alsaleem M; University of Nottingham Biodiscovery Institute, University of Nottingham, University Park, Nottingham, United Kingdom.
  • Persson JL; Department of Applied Medical Science, Applied College, Qassim University, Qassim, Saudi Arabia.
  • Gudas LJ; Department of Molecular Biology, Umeå University, Umeå, Sweden.
  • Rakha E; Department of Biomedical Sciences, Malmö Universitet, Malmö, Sweden.
  • Robinson BD; Department of Pharmacology, Weill Cornell Medicine, New York, NY, United States.
  • Khani F; University of Nottingham Biodiscovery Institute, University of Nottingham, University Park, Nottingham, United Kingdom.
  • Martin LM; Department of Urology, Weill Cornell Medicine, New York, NY, United States.
  • Moyer JE; Department of Urology, Weill Cornell Medicine, New York, NY, United States.
  • Brownlie J; Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, United States.
  • Madhusudan S; Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, United States.
  • Allegrucci C; University of Nottingham Biodiscovery Institute, University of Nottingham, University Park, Nottingham, United Kingdom.
  • James VH; University of Nottingham Biodiscovery Institute, University of Nottingham, University Park, Nottingham, United Kingdom.
  • Rutland CS; University of Nottingham Biodiscovery Institute, University of Nottingham, University Park, Nottingham, United Kingdom.
  • Fray RG; University of Nottingham Biodiscovery Institute, University of Nottingham, University Park, Nottingham, United Kingdom.
  • Ntekim A; University of Nottingham Biodiscovery Institute, University of Nottingham, University Park, Nottingham, United Kingdom.
  • de Brot S; School of Biosciences, University of Nottingham, Nottingham, United Kingdom.
  • Mongan NP; Department of Oncology, University Hospital Ibadan, Ibadan, Nigeria.
  • Jeyapalan JN; Comparative Pathology Platform (COMPATH), Institute of Animal Pathology, University of Bern, Bern, Switzerland.
Front Endocrinol (Lausanne) ; 13: 1006101, 2022.
Article en En | MEDLINE | ID: mdl-36263323
Androgen deprivation therapies (ADTs) are important treatments which inhibit androgen-induced prostate cancer (PCa) progression by either preventing androgen biosynthesis (e.g. abiraterone) or by antagonizing androgen receptor (AR) function (e.g. bicalutamide, enzalutamide, darolutamide). A major limitation of current ADTs is they often remain effective for limited durations after which patients commonly progress to a lethal and incurable form of PCa, called castration-resistant prostate cancer (CRPC) where the AR continues to orchestrate pro-oncogenic signalling. Indeed, the increasing numbers of ADT-related treatment-emergent neuroendocrine-like prostate cancers (NePC), which lack AR and are thus insensitive to ADT, represents a major therapeutic challenge. There is therefore an urgent need to better understand the mechanisms of AR action in hormone dependent disease and the progression to CRPC, to enable the development of new approaches to prevent, reverse or delay ADT-resistance. Interestingly the AR regulates distinct transcriptional networks in hormone dependent and CRPC, and this appears to be related to the aberrant function of key AR-epigenetic coregulator enzymes including the lysine demethylase 1 (LSD1/KDM1A). In this review we summarize the current best status of anti-androgen clinical trials, the potential for novel combination therapies and we explore recent advances in the development of novel epigenetic targeted therapies that may be relevant to prevent or reverse disease progression in patients with advanced CRPC.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptores Androgénicos / Neoplasias de la Próstata Resistentes a la Castración Límite: Humans / Male Idioma: En Revista: Front Endocrinol (Lausanne) Año: 2022 Tipo del documento: Article País de afiliación: Reino Unido Pais de publicación: Suiza
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptores Androgénicos / Neoplasias de la Próstata Resistentes a la Castración Límite: Humans / Male Idioma: En Revista: Front Endocrinol (Lausanne) Año: 2022 Tipo del documento: Article País de afiliación: Reino Unido Pais de publicación: Suiza