Sensitization of EGFR wild-type non-small cell lung cancer cells to EGFR-tyrosine kinase inhibitor erlotinib.

Judith Raimbourg; Marie-Pierre Joalland; Mathilde Cabart; Ludmilla De Plater; Fanny Bouquet; Ariel Savina; Didier Decaudin; Jaafar Bennouna; François Vallette; Lisenn Lalier

doi:10.1158/1535-7163.MCT-17-0075

Sensitization of EGFR wild-type non-small cell lung cancer cells to EGFR-tyrosine kinase inhibitor erlotinib.: wtEGFR non-small cell lung cancer sensitization to erlotinib

Judith Raimbourg ^{1, 2, 3} Marie-Pierre Joalland ^{2, 3, 1} Mathilde Cabart ^{2, 4, 1} Ludmilla De Plater ⁵ Fanny Bouquet ⁶ Ariel Savina ^{6, 5} Didier Decaudin ^{5, 7} Jaafar Bennouna ^{1, 2, 3} François Vallette ^{2, 3, 1, *} Lisenn Lalier ^{2, 3, 1, *}

* Auteur correspondant

1 UN - Université de Nantes

2 CRCINA - Centre de recherche de Cancérologie et d'Immunologie / Nantes - Angers

3 ICO Nantes - Institut de cancérologie de l'Ouest - Nantes

4 CRLCC Institut Bergonié

Département d'oncologie médicale

5 Laboratoire d'investigation pré-clinique/Service d'hématologie clinique

6 Laboratoire Roche SAS [Boulogne Billancourt]

7 Service d'oncologie médicale

Abstract : The benefit of EGFR-TKI in non-small cell lung cancer has been demonstrated in mutant EGFR tumors as first-line treatment but the benefit in wild-type EGFR tumors is marginal as well as restricted to maintenance therapy in pretreated patients. This work aimed at questioning the effects of cisplatin initial treatment on the EGFR pathway in non-small cell lung cancer and the functional consequences in vitro and in in vivo animal models of Patient-Derived Xenografts (PDX). We establish here that cisplatin pretreatment specifically sensitizes wild-type EGFR expressing cells to erlotinib, contrary to what happens in mutant-EGFR cells and with a blocking EGFR antibody, both in vitro and in vivo. The sensitization entails the activation of the kinase Src upstream of EGFR, thereafter transactivating EGFR through a ligand-independent activation. We propose a combination of markers which enable to discriminate between the tumors sensitized to erlotinib or not in PDX models, that should be worth testing in patients. These markers might be useful for the selection of patients who would benefit from erlotinib as a maintenance therapy.

Keywords : non-small cell lung cancer cancer chemotherapy EGFR

Type de document :

Article dans une revue

Molecular Cancer Therapeutics, American Association for Cancer Research, 2017, 16 (8), pp.1634-1644. 〈10.1158/1535-7163.MCT-17-0075〉

Domaine :

Sciences du Vivant [q-bio] / Cancer

Sciences du Vivant [q-bio] / Biologie cellulaire

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http://www.hal.inserm.fr/inserm-01525974
Contributeur : Lisenn Lalier <>
Soumis le : lundi 22 mai 2017 - 14:44:59
Dernière modification le : jeudi 5 avril 2018 - 10:37:01

cisplatin primes EGFRwt NSCLC ...

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Sensitization of EGFR wild-type non-small cell lung cancer cells to EGFR-tyrosine kinase inhibitor erlotinib.: wtEGFR non-small cell lung cancer sensitization to erlotinib

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