title: Mechanisms of Therapeutic Resistance in Prostate Cancer.
abstract: Prostate cancer is the second leading cause of cancer deaths in the USA. The challenge in managing castration-resistant prostate cancer (CRPC) stems not from the lack of therapeutic options but from the limited duration of clinical and survival benefit offered by treatments in this setting due to primary and acquired resistance. The remarkable molecular heterogeneity and tumor adaptability in advanced prostate cancer necessitate optimization of such treatment strategies. While the future of CRPC management will involve newer targeted therapies in deliberately biomarker-selected patients, interventions using current approaches may exhibit improved clinical benefit if employed in the context of optimal sequencing and combinations. This review outlines our current understanding of mechanisms of therapeutic resistance in progression to and after the development of castration resistance, highlighting targetable and reversible mechanisms of resistance.
authors.affiliation: Departments of Urology, Molecular and Cellular Biochemistry, Pathology and Toxicology and Cancer Biology, University of Kentucky College of Medicine, 800 Rose Street, Lexington, KY, 40536, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Nakazawa
authors.affiliation: The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Channing
authors.initials: C
authors.lastname: Paller
authors.affiliation: Departments of Urology, Molecular and Cellular Biochemistry, Pathology and Toxicology and Cancer Biology, University of Kentucky College of Medicine, 800 Rose Street, Lexington, KY, 40536, USA. nkypr2@email.uky.edu.
authors.forename: Natasha
authors.initials: N
authors.lastname: Kyprianou
mesh_terms: D000726:Androgen Antagonists / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics*; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D006801:Humans; D008297:Male; D058990:Molecular Targeted Therapy; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology
chemical_list: D000726:Androgen Antagonists; D014408:Biomarkers, Tumor
keywords: Castration-resistant prostate cancer; Prostate cancer; Therapeutic resistance