Castrate-resistant prostate cancer response to taxane is determined by an HNF1-dependent apoptosis resistance circuit.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
  • Additional Information
    • Source:
      Publisher: Cell Press Country of Publication: United States NLM ID: 101766894 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2666-3791 (Electronic) Linking ISSN: 26663791 NLM ISO Abbreviation: Cell Rep Med Subsets: MEDLINE
    • Publication Information:
      Original Publication: [Cambridge, MA] : Cell Press, [2020]-
    • Subject Terms:
    • Abstract:
      Metastatic castrate-resistant prostate cancer (mCRPC) is a genetically and phenotypically heterogeneous cancer where advancements are needed in biomarker discovery and targeted therapy. A critical and often effective component of treatment includes taxanes. We perform a high-throughput screen across a cohort of 30 diverse patient-derived castrate-resistant prostate cancer (CRPC) organoids to a library of 78 drugs. Combining quantitative response measures with transcriptomic analyses demonstrates that HNF1 homeobox A (HNF1A) drives a transcriptional program of taxane resistance, commonly dependent upon cellular inhibitor of apoptosis protein 2 (cIAP2). Monotherapy with cIAP2 inhibitor LCL161 is sufficient to treat HNF1A+ models of mCRPC previously resistant to docetaxel. These data may be useful in future clinical trial designs.
      Competing Interests: Declaration of interests E.C. received sponsored research funding from Sanofi, Gilead, AbbVie, Genentech, Janssen Research, AstraZeneca, GSK, Bayer Pharmaceuticals, Forma Pharmaceuticals, Foghorn, Kronos, and MarcoGenics.
      (Published by Elsevier Inc.)
    • References:
      Cancer Res. 2010 Oct 15;70(20):7992-8002. (PMID: 20807808)
      Nat Med. 2016 Apr;22(4):369-78. (PMID: 26928463)
      Nat Commun. 2022 Apr 21;13(1):2177. (PMID: 35449130)
      Nat Med. 2015 Nov;21(11):1318-25. (PMID: 26479923)
      Proc Natl Acad Sci U S A. 2002 May 14;99(10):6567-72. (PMID: 12011421)
      N Engl J Med. 2004 Oct 7;351(15):1513-20. (PMID: 15470214)
      Cancer Discov. 2018 Sep;8(9):1112-1129. (PMID: 29853643)
      JAMA. 2017 Jun 27;317(24):2532-2542. (PMID: 28655021)
      Lancet Oncol. 2004 Mar;5(3):158-64. (PMID: 15003198)
      Cancer Cell. 2017 Dec 11;32(6):792-806.e7. (PMID: 29153843)
      Nat Rev Drug Discov. 2006 Mar;5(3):219-34. (PMID: 16518375)
      Clin Cancer Res. 2018 Sep 1;24(17):4332-4345. (PMID: 29748182)
      Nature. 2006 Jan 19;439(7074):353-7. (PMID: 16273092)
      Mol Cancer Ther. 2015 Nov;14(11):2569-75. (PMID: 26333381)
      J Clin Invest. 2010 Dec;120(12):4478-92. (PMID: 21099110)
      Biochim Biophys Acta. 2001;1471(2):O1-9. (PMID: 11342188)
      J Clin Invest. 2020 Jun 1;130(6):3287-3298. (PMID: 32478682)
      Nat Rev Cancer. 2015 Dec;15(12):701-11. (PMID: 26563462)
      Drug Healthc Patient Saf. 2011;3:107-19. (PMID: 22279415)
      Cancer Med. 2023 Jul;12(13):13958-13965. (PMID: 37132167)
      BMC Med Genomics. 2020 Jan 21;13(1):7. (PMID: 31964418)
      Am J Clin Exp Urol. 2019 Aug 15;7(4):223-231. (PMID: 31511829)
      Science. 2022 May 27;376(6596):eabe1505. (PMID: 35617398)
      Nat Genet. 2017 Nov;49(11):1567-1575. (PMID: 28991255)
      Proc Natl Acad Sci U S A. 2019 Jun 4;116(23):11428-11436. (PMID: 31061129)
      Clin Cancer Res. 2022 Feb 15;28(4):708-718. (PMID: 34789479)
      BMC Genomics. 2013 Nov 11;14:778. (PMID: 24215113)
      Int J Oncol. 2002 Sep;21(3):621-8. (PMID: 12168109)
      Cancer Cell. 2008 Aug 12;14(2):111-22. (PMID: 18656424)
      NPJ Precis Oncol. 2021 Apr 12;5(1):30. (PMID: 33846504)
      Nat Rev Clin Oncol. 2012 Apr 17;9(6):338-50. (PMID: 22508028)
      Nat Protoc. 2016 Feb;11(2):347-58. (PMID: 26797458)
      Cancer Res. 2014 Apr 15;74(8):2270-2282. (PMID: 24556717)
      Cell Syst. 2018 Nov 28;7(5):548-555.e8. (PMID: 30448000)
      Cancer Res. 2011 Sep 15;71(18):6019-29. (PMID: 21799031)
      N Engl J Med. 2004 Oct 7;351(15):1502-12. (PMID: 15470213)
      Nat Med. 2016 Mar;22(3):298-305. (PMID: 26855148)
      CA Cancer J Clin. 2023 Jan;73(1):17-48. (PMID: 36633525)
      Cancer Res. 2010 Nov 15;70(22):9253-64. (PMID: 21045157)
      Oncoscience. 2015 Sep 01;2(8):703-15. (PMID: 26425662)
      Nat Rev Cancer. 2017 Apr;17(4):254-268. (PMID: 28104906)
      Clin Cancer Res. 2020 Jun 15;26(12):2819-2826. (PMID: 31900279)
      J Natl Compr Canc Netw. 2019 May 1;17(5):479-505. (PMID: 31085757)
      Mol Cancer Ther. 2013 Sep;12(9):1829-36. (PMID: 23861346)
      Cancer Cell. 2019 Jul 8;36(1):17-34.e7. (PMID: 31287989)
      Trends Pharmacol Sci. 1992 Apr;13(4):134-6. (PMID: 1350385)
      J Clin Oncol. 2017 Oct 1;35(28):3189-3197. (PMID: 28753384)
      Am J Pathol. 1996 May;148(5):1567-76. (PMID: 8623925)
      Mol Cancer. 2010 Jan 19;9:9. (PMID: 20085644)
      Sci Rep. 2018 May 25;8(1):8161. (PMID: 29802284)
      Nat Commun. 2017 Feb 10;8:14262. (PMID: 28186126)
      Prostate. 2009 Sep 15;69(13):1448-59. (PMID: 19496068)
      Cancer Cell. 2017 Oct 9;32(4):474-489.e6. (PMID: 29017058)
      Prostate. 2017 May;77(6):654-671. (PMID: 28156002)
      J Clin Invest. 2023 Nov 15;133(22):. (PMID: 37725435)
    • Contributed Indexing:
      Keywords: BIRC3; HNF1A; apoptosis; docetaxel; drug resistance; organoid; pharmacology; prostate cancer; xenograft
    • Accession Number:
      0 (Taxoids)
      0 (Hepatocyte Nuclear Factor 1-alpha)
      1605-68-1 (taxane)
      0 (HNF1A protein, human)
      EC 2.3.2.27 (Baculoviral IAP Repeat-Containing 3 Protein)
      0 (Bridged-Ring Compounds)
      15H5577CQD (Docetaxel)
    • Publication Date:
      Date Created: 20241210 Date Completed: 20241218 Latest Revision: 20250112
    • Publication Date:
      20250112
    • Accession Number:
      PMC11722106
    • Accession Number:
      10.1016/j.xcrm.2024.101868
    • Accession Number:
      39657662