Development of transplantable human chordoma xenograft for preclinical assessment of novel therapeutic strategies

Fabio Bozzi, Giacomo Manenti, Elena Conca, Silvia Stacchiotti, Antonella Messina, GianPaolo Dagrada, Alessandro Gronchi, Pietro Panizza, Marco A. Pierotti, Elena Tamborini, Silvana Pilotti

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

BackgroundChordomas are rare and indolent bone tumors that arise in the skull base and mobile spine. Distant metastases occur in >20% of cases, but morbidity and mortality are mainly related to local relapses that affect the majority of patients. Standard chemotherapy has modest activity, whereas new targeted therapies (alone or in combination) have some activity in controlling disease progression. However, the scarcity of preclinical models capable of testing in vivo responses to these therapies hampers the development of new medical strategies.MethodsIn this study, 8 chordoma samples taken from 8 patients were implanted in nude mice. Four engrafted successfully and gave rise to tumor masses that were analyzed histologically, by means of fluorescence in situ hybridization and biochemical techniques. The data relating to each of the mouse tumors were compared with those obtained from the corresponding human tumor.ResultsAll 4 engraftments retained the histological, genetic and biochemical features of the human tumors they came from. In one epidermal growth factor receptor(EGFR)-positive xenograft, responsiveness to lapatinib was evaluated by comparing the pre- and posttreatment findings. The treatment induced a low-level, heterogeneous switching off of EGFR and its downstream signaling effectors.ConclusionsOverall, this model is very close to human chordoma and represents a new means of undertaking preclinical investigations and developing tailored therapies.

Original languageEnglish
Pages (from-to)72-80
Number of pages9
JournalNeuro-Oncology
Volume16
Issue number1
DOIs
Publication statusPublished - 2014

Fingerprint

Chordoma
Human Development
Heterografts
Neoplasms
Epidermal Growth Factor Receptor
Therapeutics
Skull Base
Fluorescence In Situ Hybridization
Nude Mice
Disease Progression
Molecular Biology
Spine
Neoplasm Metastasis
Morbidity
Bone and Bones
Recurrence
Drug Therapy
Mortality

Keywords

  • chordoma
  • EGFR
  • preclinical model
  • tailored therapies

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Clinical Neurology

Cite this

Development of transplantable human chordoma xenograft for preclinical assessment of novel therapeutic strategies. / Bozzi, Fabio; Manenti, Giacomo; Conca, Elena; Stacchiotti, Silvia; Messina, Antonella; Dagrada, GianPaolo; Gronchi, Alessandro; Panizza, Pietro; Pierotti, Marco A.; Tamborini, Elena; Pilotti, Silvana.

In: Neuro-Oncology, Vol. 16, No. 1, 2014, p. 72-80.

Research output: Contribution to journalArticle

@article{d797719210614af4a77b38ca65e24f65,
title = "Development of transplantable human chordoma xenograft for preclinical assessment of novel therapeutic strategies",
abstract = "BackgroundChordomas are rare and indolent bone tumors that arise in the skull base and mobile spine. Distant metastases occur in >20{\%} of cases, but morbidity and mortality are mainly related to local relapses that affect the majority of patients. Standard chemotherapy has modest activity, whereas new targeted therapies (alone or in combination) have some activity in controlling disease progression. However, the scarcity of preclinical models capable of testing in vivo responses to these therapies hampers the development of new medical strategies.MethodsIn this study, 8 chordoma samples taken from 8 patients were implanted in nude mice. Four engrafted successfully and gave rise to tumor masses that were analyzed histologically, by means of fluorescence in situ hybridization and biochemical techniques. The data relating to each of the mouse tumors were compared with those obtained from the corresponding human tumor.ResultsAll 4 engraftments retained the histological, genetic and biochemical features of the human tumors they came from. In one epidermal growth factor receptor(EGFR)-positive xenograft, responsiveness to lapatinib was evaluated by comparing the pre- and posttreatment findings. The treatment induced a low-level, heterogeneous switching off of EGFR and its downstream signaling effectors.ConclusionsOverall, this model is very close to human chordoma and represents a new means of undertaking preclinical investigations and developing tailored therapies.",
keywords = "chordoma, EGFR, preclinical model, tailored therapies",
author = "Fabio Bozzi and Giacomo Manenti and Elena Conca and Silvia Stacchiotti and Antonella Messina and GianPaolo Dagrada and Alessandro Gronchi and Pietro Panizza and Pierotti, {Marco A.} and Elena Tamborini and Silvana Pilotti",
year = "2014",
doi = "10.1093/neuonc/not152",
language = "English",
volume = "16",
pages = "72--80",
journal = "Neuro-Oncology",
issn = "1522-8517",
publisher = "Oxford University Press",
number = "1",

}

TY - JOUR

T1 - Development of transplantable human chordoma xenograft for preclinical assessment of novel therapeutic strategies

AU - Bozzi, Fabio

AU - Manenti, Giacomo

AU - Conca, Elena

AU - Stacchiotti, Silvia

AU - Messina, Antonella

AU - Dagrada, GianPaolo

AU - Gronchi, Alessandro

AU - Panizza, Pietro

AU - Pierotti, Marco A.

AU - Tamborini, Elena

AU - Pilotti, Silvana

PY - 2014

Y1 - 2014

N2 - BackgroundChordomas are rare and indolent bone tumors that arise in the skull base and mobile spine. Distant metastases occur in >20% of cases, but morbidity and mortality are mainly related to local relapses that affect the majority of patients. Standard chemotherapy has modest activity, whereas new targeted therapies (alone or in combination) have some activity in controlling disease progression. However, the scarcity of preclinical models capable of testing in vivo responses to these therapies hampers the development of new medical strategies.MethodsIn this study, 8 chordoma samples taken from 8 patients were implanted in nude mice. Four engrafted successfully and gave rise to tumor masses that were analyzed histologically, by means of fluorescence in situ hybridization and biochemical techniques. The data relating to each of the mouse tumors were compared with those obtained from the corresponding human tumor.ResultsAll 4 engraftments retained the histological, genetic and biochemical features of the human tumors they came from. In one epidermal growth factor receptor(EGFR)-positive xenograft, responsiveness to lapatinib was evaluated by comparing the pre- and posttreatment findings. The treatment induced a low-level, heterogeneous switching off of EGFR and its downstream signaling effectors.ConclusionsOverall, this model is very close to human chordoma and represents a new means of undertaking preclinical investigations and developing tailored therapies.

AB - BackgroundChordomas are rare and indolent bone tumors that arise in the skull base and mobile spine. Distant metastases occur in >20% of cases, but morbidity and mortality are mainly related to local relapses that affect the majority of patients. Standard chemotherapy has modest activity, whereas new targeted therapies (alone or in combination) have some activity in controlling disease progression. However, the scarcity of preclinical models capable of testing in vivo responses to these therapies hampers the development of new medical strategies.MethodsIn this study, 8 chordoma samples taken from 8 patients were implanted in nude mice. Four engrafted successfully and gave rise to tumor masses that were analyzed histologically, by means of fluorescence in situ hybridization and biochemical techniques. The data relating to each of the mouse tumors were compared with those obtained from the corresponding human tumor.ResultsAll 4 engraftments retained the histological, genetic and biochemical features of the human tumors they came from. In one epidermal growth factor receptor(EGFR)-positive xenograft, responsiveness to lapatinib was evaluated by comparing the pre- and posttreatment findings. The treatment induced a low-level, heterogeneous switching off of EGFR and its downstream signaling effectors.ConclusionsOverall, this model is very close to human chordoma and represents a new means of undertaking preclinical investigations and developing tailored therapies.

KW - chordoma

KW - EGFR

KW - preclinical model

KW - tailored therapies

UR - http://www.scopus.com/inward/record.url?scp=84891513524&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84891513524&partnerID=8YFLogxK

U2 - 10.1093/neuonc/not152

DO - 10.1093/neuonc/not152

M3 - Article

VL - 16

SP - 72

EP - 80

JO - Neuro-Oncology

JF - Neuro-Oncology

SN - 1522-8517

IS - 1

ER -