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Bull Cancer. 2018 Jan;105(1):35-45. doi: 10.1016/j.bulcan.2017.11.007. Epub 2017 Dec 23.

[Molecular heterogeneity of malignant pleural mesotheliomas].

[Article in French]

Author information

1
Inserm, UMR-1162, génomique fonctionnelle des tumeurs solides, équipe 1 « Génomique des tumeurs hépatiques et mésothéliales », 75010 Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Labex Immuno-oncology, 12, rue de l'école de Médecine, 75006 Paris, France; Université Paris Diderot, Sorbonne Paris Cité, institut universitaire d'hématologie, 10, avenue de Verdun, 75010 Paris, France; Université Paris 13, Sorbonne Paris Cité, 35, rue Auguste-Poullain, 93206 Saint-Denis, France.
2
Inserm, UMR-1162, génomique fonctionnelle des tumeurs solides, équipe 1 « Génomique des tumeurs hépatiques et mésothéliales », 75010 Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Labex Immuno-oncology, 12, rue de l'école de Médecine, 75006 Paris, France; Université Paris Diderot, Sorbonne Paris Cité, institut universitaire d'hématologie, 10, avenue de Verdun, 75010 Paris, France; Université Paris 13, Sorbonne Paris Cité, 35, rue Auguste-Poullain, 93206 Saint-Denis, France; CHRU de Lille, hôpital Calmette, service de chirurgie thoracique, 2, avenue Oscar-Lambret, 59000 Lille, France; Université droit et santé Lille 2, 59000 Lille, France.
3
Inserm, UMR-1162, génomique fonctionnelle des tumeurs solides, équipe 1 « Génomique des tumeurs hépatiques et mésothéliales », 75010 Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Labex Immuno-oncology, 12, rue de l'école de Médecine, 75006 Paris, France; Université Paris Diderot, Sorbonne Paris Cité, institut universitaire d'hématologie, 10, avenue de Verdun, 75010 Paris, France; Université Paris 13, Sorbonne Paris Cité, 35, rue Auguste-Poullain, 93206 Saint-Denis, France. Electronic address: didier.jean@inserm.fr.

Abstract

Malignant pleural mesothelioma (MPM) is predominantly an occupational cancer, most often linked to asbestos exposure. Malignant pleural mesothelioma prognosis is poor with a short survival median, due to the aggressiveness of tumor cells and the weak efficiency of conventional anti-cancer therapies. Clinical, histological, and molecular data suggest tumor heterogeneity between patients as it was also shown for other cancer types. Consequently, there is an urgent need to develop new therapies that take into account this heterogeneity and the molecular characteristics of malignant pleural mesothelioma, in particular by identifying new anti-cancer drugs targeting the molecular specificities of each malignant pleural mesothelioma. Malignant pleural mesothelioma is characterized by numerous molecular alterations at the chromosomal, genetic and epigenetic levels. Molecular classification based on gene expression profile has firstly defined two tumor groups, C1 and C2, and more recently, four groups. By integrating genetic and transcriptomic analysis, a C2LN tumor subgroup of the C2 group has been identified and characterized. In addition to tumor heterogeneity between patients, intra-tumor heterogeneity is supported by several evidences. Most therapeutic strategies that take into account the tumor molecular characteristics have focused on targeted therapies based on mutated genes. A more appropriate strategy would be to consider better-defined tumor groups on the basis of several molecular alterations types as it has been proposed for the C2LN subgroup. A robust definition of homogeneous tumor groups sharing common molecular characteristics is necessary for the development of effective precision medicine for malignant pleural mesothelioma.

KEYWORDS:

Altération moléculaire; Cancer thoracique; Genomic; Génomique; Hétérogénéité tumorale; Malignant pleural mesothelioma; Molecular alteration; Médecine de précision; Mésothéliome pleural malin; Precision medicine; Thoracic cancer; Tumor heterogeneity

PMID:
29277245
DOI:
10.1016/j.bulcan.2017.11.007
[Indexed for MEDLINE]

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