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Sökning: id:"swepub:oai:DiVA.org:liu-183231" > Zebrafish patient-d...

  • Ali, ZaheerBioReperia AB, Linkoping, Sweden (författare)

Zebrafish patient-derived xenograft models predict lymph node involvement and treatment outcome in non-small cell lung cancer

  • Artikel/kapitelEngelska2022

Förlag, utgivningsår, omfång ...

  • 2022-02-09
  • BMC,2022
  • electronicrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:liu-183231
  • https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-183231URI
  • https://doi.org/10.1186/s13046-022-02280-xDOI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • Funding Agencies|Linkoping University; H2020-MCSA-RISE-3DNEONET; H2020-MSCA-RISE-CRYSTAL3; VINNOVAVinnova
  • Background Accurate predictions of tumor dissemination risks and medical treatment outcomes are critical to personalize therapy. Patient-derived xenograft (PDX) models in mice have demonstrated high accuracy in predicting therapeutic outcomes, but methods for predicting tumor invasiveness and early stages of vascular/lymphatic dissemination are still lacking. Here we show that a zebrafish tumor xenograft (ZTX) platform based on implantation of PDX tissue fragments recapitulate both treatment outcome and tumor invasiveness/dissemination in patients, within an assay time of only 3 days. Methods Using a panel of 39 non-small cell lung cancer PDX models, we developed a combined mouse-zebrafish PDX platform based on direct implantation of cryopreserved PDX tissue fragments into zebrafish embryos, without the need for pre-culturing or expansion. Clinical proof-of-principle was established by direct implantation of tumor samples from four patients. Results The resulting ZTX models responded to Erlotinib and Paclitaxel, with similar potency as in mouse-PDX models and the patients themselves, and resistant tumors similarly failed to respond to these drugs in the ZTX system. Drug response was coupled to elevated expression of EGFR, Mdm2, Ptch1 and Tsc1 (Erlotinib), or Nras and Ptch1 (Paclitaxel) and reduced expression of Egfr, Erbb2 and Foxa (Paclitaxel). Importantly, ZTX models retained the invasive phenotypes of the tumors and predicted lymph node involvement of the patients with 91% sensitivity and 62% specificity, which was superior to clinically used tests. The biopsies from all four patient tested implanted successfully, and treatment outcome and dissemination were quantified for all patients in only 3 days. Conclusions We conclude that the ZTX platform provide a fast, accurate, and clinically relevant system for evaluation of treatment outcome and invasion/dissemination of PDX models, providing an attractive platform for combined mouse-zebrafish PDX trials and personalized medicine.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Vildevall, MalinBioReperia AB, Linkoping, Sweden (författare)
  • Rodriguez, Gabriela VazquezBioReperia AB, Linkoping, Sweden (författare)
  • Tandiono, DeckyBioReperia AB, Linkoping, Sweden (författare)
  • Vamvakaris, IoannisAthens Chest Hosp Sotiria, Greece (författare)
  • Evangelou, GeorgiosNatl Kapodistrian Univ Athens, Greece (författare)
  • Lolas, GeorgiosNatl Kapodistrian Univ Athens, Greece; Catalan Inst Oncol ICO, Spain (författare)
  • Syrigos, Konstantinos N.Natl Kapodistrian Univ Athens, Greece (författare)
  • Villanueva, AlbertoInCELLiA PC, Greece; Xenopat SL, Spain (författare)
  • Wick, MichaelXenoSTART, TX USA (författare)
  • Omar, ShengaLinköpings universitet,Avdelningen för diagnostik och specialistmedicin,Medicinska fakulteten(Swepub:liu)n/a (författare)
  • Erkstam, AnnaBioReperia AB, Linkoping, Sweden (författare)
  • Schueler, JuliaCharles River Labs, Germany (författare)
  • Fahlgren, AnnaLinköpings universitet,Avdelningen för cellbiologi,Medicinska fakulteten,BioReperia AB, Linkoping, Sweden(Swepub:liu)annfa39 (författare)
  • Jensen, LasseLinköpings universitet,Avdelningen för diagnostik och specialistmedicin,Medicinska fakulteten,Region Östergötland, Klinisk farmakologi,BioReperia AB, Linkoping, Sweden(Swepub:liu)larje86 (författare)
  • BioReperia AB, Linkoping, SwedenAthens Chest Hosp Sotiria, Greece (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Journal of Experimental & Clinical Cancer Research: BMC41:11756-9966

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