Your browser doesn't support javascript.
loading
Transcriptional mediators of treatment resistance in lethal prostate cancer.
He, Meng Xiao; Cuoco, Michael S; Crowdis, Jett; Bosma-Moody, Alice; Zhang, Zhenwei; Bi, Kevin; Kanodia, Abhay; Su, Mei-Ju; Ku, Sheng-Yu; Garcia, Maria Mica; Sweet, Amalia R; Rodman, Christopher; DelloStritto, Laura; Silver, Rebecca; Steinharter, John; Shah, Parin; Izar, Benjamin; Walk, Nathan C; Burke, Kelly P; Bakouny, Ziad; Tewari, Alok K; Liu, David; Camp, Sabrina Y; Vokes, Natalie I; Salari, Keyan; Park, Jihye; Vigneau, Sébastien; Fong, Lawrence; Russo, Joshua W; Yuan, Xin; Balk, Steven P; Beltran, Himisha; Rozenblatt-Rosen, Orit; Regev, Aviv; Rotem, Asaf; Taplin, Mary-Ellen; Van Allen, Eliezer M.
Afiliação
  • He MX; Harvard Graduate Program in Biophysics, Boston, MA, USA.
  • Cuoco MS; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Crowdis J; Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Bosma-Moody A; Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Zhang Z; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Bi K; Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Kanodia A; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Su MJ; Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Ku SY; Harvard Medical School, Boston, MA, USA.
  • Garcia MM; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Sweet AR; Department of Pathology, University of Massachusetts Memorial Medical Center, Worcester, MA, USA.
  • Rodman C; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • DelloStritto L; Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Silver R; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Steinharter J; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Shah P; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Izar B; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Walk NC; Department of Medicine, Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
  • Burke KP; Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Bakouny Z; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Tewari AK; Center for Cancer Genomics, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Liu D; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Camp SY; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Vokes NI; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Salari K; Columbia Center for Translational Immunology, New York, NY, USA.
  • Park J; Department of Medicine, Division of Hematology/Oncology, Columbia University Medical Center, New York, NY, USA.
  • Vigneau S; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Fong L; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Russo JW; Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
  • Yuan X; Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA.
  • Balk SP; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Beltran H; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Rozenblatt-Rosen O; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Regev A; Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Rotem A; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Taplin ME; Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Van Allen EM; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Nat Med ; 27(3): 426-433, 2021 03.
Article em En | MEDLINE | ID: mdl-33664492
ABSTRACT
Metastatic castration-resistant prostate cancer is typically lethal, exhibiting intrinsic or acquired resistance to second-generation androgen-targeting therapies and minimal response to immune checkpoint inhibitors1. Cellular programs driving resistance in both cancer and immune cells remain poorly understood. We present single-cell transcriptomes from 14 patients with advanced prostate cancer, spanning all common metastatic sites. Irrespective of treatment exposure, adenocarcinoma cells pervasively coexpressed multiple androgen receptor isoforms, including truncated isoforms hypothesized to mediate resistance to androgen-targeting therapies2,3. Resistance to enzalutamide was associated with cancer cell-intrinsic epithelial-mesenchymal transition and transforming growth factor-ß signaling. Small cell carcinoma cells exhibited divergent expression programs driven by transcriptional regulators promoting lineage plasticity and HOXB5, HOXB6 and NR1D2 (refs. 4-6). Additionally, a subset of patients had high expression of dysfunction markers on cytotoxic CD8+ T cells undergoing clonal expansion following enzalutamide treatment. Collectively, the transcriptional characterization of cancer and immune cells from human metastatic castration-resistant prostate cancer provides a basis for the development of therapeutic approaches complementing androgen signaling inhibition.
Assuntos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Transcrição Gênica / Neoplasias de Próstata Resistentes à Castração / Antineoplásicos Limite: Humans / Male Idioma: En Ano de publicação: 2021 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Transcrição Gênica / Neoplasias de Próstata Resistentes à Castração / Antineoplásicos Limite: Humans / Male Idioma: En Ano de publicação: 2021 Tipo de documento: Article