title: Addressing taxane resistance in metastatic castration-resistant prostate cancer: a focus on chaperone proteins.
abstract: Despite the significant survival benefit of taxane therapy in metastatic castration-resistant prostate cancer (mCRPC), all patients inevitably develop treatment resistance. An understanding of resistance mechanisms has led to new therapies for prostate cancer (cabazitaxel, abiraterone and enzalutamide), all of which have improved survival following first-line docetaxel. Another treatment, currently in development, targets the prosurvival molecule clusterin. Custirsen, an antisense molecule that inhibits clusterin production, has shown promise in combination with docetaxel in mCRPC patients at risk for poor outcomes. Although optimal sequence and combination of available therapies is unclear, the heterogeneity of mCRPC suggests a continuing need for personalized treatment regimens and improved abilities to predict which patients will respond to the available treatment options.
authors.affiliation: Department of Oncology, Division of Medical Oncology, Juravinski Cancer Centre, 699 Concession Street, Hamilton, Ontario, L8V 5C2, Canada.
authors.forename: Sebastien J
authors.initials: SJ
authors.lastname: Hotte
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001952:Bridged-Ring Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D008297:Male; D008870:Microtubules / Q000235:genetics / Q000378:metabolism; D018832:Molecular Chaperones / Q000378:metabolism; D009362:Neoplasm Metastasis; D018579:Patient Selection; D011379:Prognosis; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D011944:Receptors, Androgen / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D043823:Taxoids / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001952:Bridged-Ring Compounds; D018832:Molecular Chaperones; D011944:Receptors, Androgen; D043823:Taxoids; C080625:taxane
keywords: androgen receptor axis; apoptosis; chemotherapy; custirsen; drug sequencing; metastatic castration-resistant prostate cancer; prognostic factors; taxane resistance