Establishment of novel cell lines recapitulating the genetic landscape of uveal melanoma and preclinical validation of mTOR as a therapeutic target

Nabil Amirouchene-Angelozzi, Fariba Nemati, David Gentien, André Nicolas, Amaury Dumont, Guillaume Carita, Jacques Camonis, Laurence Desjardins, Nathalie Cassoux, Sophie Piperno-Neumann, Pascale Mariani, Xavier Sastre, Didier Decaudin, Sergio Roman-Roman

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Uveal melanoma (UM) is the most common primary tumor of the eye in adults. There is no standard adjuvant treatment to prevent metastasis and no effective therapy in the metastatic setting. We have established a unique panel of 7 UM cell lines from either patient's tumors or patient-derived tumor xenografts (PDXs). This panel recapitulates the molecular landscape of the disease in terms of genetic alterations and mutations. All the cell lines display GNAQ or GNA11 activating mutations, and importantly four of them display BAP1 (BRCA1 associated protein-1) deficiency, a hallmark of aggressive disease. The mTOR pathway was shown to be activated in most of the cell lines independent of AKT signaling. mTOR inhibitor Everolimus reduced the viability of UM cell lines and significantly delayed tumor growth in 4 PDXs. Our data suggest that mTOR inhibition with Everolimus, possibly in combination with other agents, may be considered as a therapeutic option for the management of uveal melanoma.

Original languageEnglish
Pages (from-to)1508-1520
Number of pages13
JournalMolecular Oncology
Volume8
Issue number8
DOIs
Publication statusPublished - Dec 1 2014

Fingerprint

Cell Line
Neoplasms
Heterografts
BRCA1 Protein
Therapeutics
Protein Deficiency
Mutation
Uveal melanoma
Neoplasm Metastasis
Growth
Everolimus

Keywords

  • BAP1
  • Cell lines
  • Everolimus
  • MTOR
  • Patients-derived tumor xenografts
  • Uveal melanoma

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Molecular Medicine

Cite this

Establishment of novel cell lines recapitulating the genetic landscape of uveal melanoma and preclinical validation of mTOR as a therapeutic target. / Amirouchene-Angelozzi, Nabil; Nemati, Fariba; Gentien, David; Nicolas, André; Dumont, Amaury; Carita, Guillaume; Camonis, Jacques; Desjardins, Laurence; Cassoux, Nathalie; Piperno-Neumann, Sophie; Mariani, Pascale; Sastre, Xavier; Decaudin, Didier; Roman-Roman, Sergio.

In: Molecular Oncology, Vol. 8, No. 8, 01.12.2014, p. 1508-1520.

Research output: Contribution to journalArticle

Amirouchene-Angelozzi, N, Nemati, F, Gentien, D, Nicolas, A, Dumont, A, Carita, G, Camonis, J, Desjardins, L, Cassoux, N, Piperno-Neumann, S, Mariani, P, Sastre, X, Decaudin, D & Roman-Roman, S 2014, 'Establishment of novel cell lines recapitulating the genetic landscape of uveal melanoma and preclinical validation of mTOR as a therapeutic target', Molecular Oncology, vol. 8, no. 8, pp. 1508-1520. https://doi.org/10.1016/j.molonc.2014.06.004
Amirouchene-Angelozzi, Nabil ; Nemati, Fariba ; Gentien, David ; Nicolas, André ; Dumont, Amaury ; Carita, Guillaume ; Camonis, Jacques ; Desjardins, Laurence ; Cassoux, Nathalie ; Piperno-Neumann, Sophie ; Mariani, Pascale ; Sastre, Xavier ; Decaudin, Didier ; Roman-Roman, Sergio. / Establishment of novel cell lines recapitulating the genetic landscape of uveal melanoma and preclinical validation of mTOR as a therapeutic target. In: Molecular Oncology. 2014 ; Vol. 8, No. 8. pp. 1508-1520.
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