Establishment and characterisation of a new patient-derived model of myxoid liposarcoma with acquired resistance to trabectedin

Ezia Bello, Silvia Brich, Ilaria Craparotta, Laura Mannarino, Sara Ballabio, Raffaella Gatta, Sergio Marchini, Laura Carrassa, Cristina Matteo, Roberta Sanfilippo, Alessandro Gronchi, Paolo Giovanni Casali, Silvana Pilotti, Maurizio D’Incalci, Roberta Frapolli

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Myxoid liposarcoma is a histological subtype of liposarcoma particularly sensitive to trabectedin. In clinical use this drug does not cause cumulative toxicity, allowing prolonged treatment, generally until disease progression. No other effective therapies are available for trabectedin-resistant patients. Methods: Through repeated in vivo treatment in athymic nude mice, we have obtained a patient-derived xenograft with acquired resistance to trabectedin. Results: At basal level, the morphology of the resistant and sensitive models did not differ, in keeping with the finding that the transcriptional profiles of the resistant and sensitive tumours were very similar. After trabectedin treatment adipogenesis was induced in the parental xenograft but not in the resistant one, as assessed by pathological and molecular analysis. A defective transcription-coupled-nucleotide excision repair in the resistant tumour due to mutation of the UVSSA gene may be implicated in the mechanism of resistance. Conclusions: This is the first in vivo model of myxoid liposarcoma with acquired resistance to trabectedin. Although further studies are necessary to characterise the resistance mechanisms, this is a useful tool for studying new therapeutic strategies to overcome trabectedin resistance in patients.

Original languageEnglish
Pages (from-to)464-473
Number of pages10
JournalBritish Journal of Cancer
Volume121
Issue number6
DOIs
Publication statusPublished - Sep 10 2019

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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