Research
Oncogenic pathways in lung cancer : A. Maraver

Oncogenic pathways in lung cancer (IRCM teams)

Team Leader  : Antonio Maraver
 
Institut de Recherche en
Cancérologie de Montpellier
Campus Val d’Aurelle
34298 Montpellier cedex 5

 
Tél. : 33 (0)4 67 61 23 95
Fax : 33 (0)4 67 61 37 87
antonio.maraver@inserm.fr
 
Research topics
    

Lung cancer kills about a million people every year worldwide being the leading cause of death by cancer in the world. Oncogenic addiction has been therapeutically exploited in a subset of lung adenocarcinoma patients harboring genetic alterations in different oncogenes such as EGFR, ALK, MET, ROS, or RET thanks to the development of tyrosine kinase inhibitor (TKIs). Although these patients have in general a good initial response they always develop resistance by a plethora of mechanisms including new mutations, also called gatekeeper mutations. At this stage there is only conventional platin-based chemotherapy to offer to the patients, but also rapidly develop resistance against this treatment.

 

Using state-of the art lung cancer genetic engineered mouse models (some of them unique to our laboratory), lung cancer patient-derived xenografts, as well as clinical samples, our group endeavors to tackle resistance to all these treatments in lung adenocarcinoma by combining the inhibition of oncogen addiction, trough the use of different tyrosine kinase inhibitors, and of non-oncogen addiction, by using the Notch pathway as an example. The major objective is to establish rational combination therapies with the final goal of developing clinical trials at our local hospital, ICM.

 

 

more information ...
 
 
Main Publications

 

Mancini M, Gal H, Gaborit N, Mazzeo L, Romaniello D, Salame TM, Lindzen M, Mahlknecht G, Enuka Y, Burton DG, Roth L, Noronha A, Marrocco I, Adreka D, Altstadter RE, Bousquet E, Downward J, Maraver A, Krizhanovsky V, Yarden Y. An oligoclonal antibody durably overcomes resistance of lung cancer to third-generation EGFR inhibitors. EMBO Mol Med. 2017 Dec 6. pii: e201708076. doi: 10.15252/ emmm.201708076. [Epub ahead of print]

 

Calvayrac O, Mazières J, Figarol S, Marty-Detraves C, Raymond-Letron I, Bousquet E, Farella M, Clermont-Taranchon E, Milia J, Rouquette I, Guibert N, Lusque A, Cadranel J, Mathiot N, Savina A, Pradines A, Favre G. The RAS-related GTPase RHOB confers resistance to EGFR-tyrosine kinase inhibitors in non-small-cell lung cancer via an AKT-dependent mechanism. EMBO Mol Med. 2017 Feb;9(2):238-250. doi: 10.15252/ emmm.201606646.

 

Casas-Tintó S, Maraver A, Serrano M, Ferrús A. Troponin-I enhances and is required for oncogenic overgrowth. Oncotarget. 2016 Jul 15.  [Epub ahead of print]

 

Rivera-Torres J, Guzman G, Villa-Bellosta R, Orbe J, González-Gómez C, Serrano M, Díez J, Andres V & Maraver A. Targeting ?-secretases protects against angiotensin II-induced cardiac hypertrophy. Journal of Hypertension. 33, 843-850 (2015). #corresponding author.


Fernandez-Marcos PJ, Serrano M & Maraver A. Bladder cancer and the Notch pathway. Oncotarget (2015) Jan 26 [Epub ahead of print]. #corresponding author.


Maraver A, Fernandez-Marcos PJ, Cash T, Mendez M, Dueñas M, Maietta P, Muñoz-Martin M, Martínez-Fernández M, Canamero M, Valencia A, Grivas, D, de la Pompa JL, Paramio JM, Real FX, Serrano M. NOTCH deficiency promotes bladder cancer. Journal of Clinical Investigation. 125, 824-30 (2015). #corresponding author.


more information ...

 

SUMMARY

Lung cancer kills about a million people every year worldwide being the leading cause of death by cancer in the world. Oncogenic addiction has been therapeutically exploited in a subset of lung adenocarcinoma patients harboring genetic alterations in different oncogenes such as EGFR, ALK, MET, ROS, or RET thanks to the development of tyrosine kinase inhibitor (TKIs). Although these patients have in general a good initial response they always develop resistance by a plethora of mechanisms including new mutations, also called gatekeeper mutations. At this stage there is only conventional platin-based chemotherapy to offer to the patients, but also rapidly develop resistance against this treatment.

Using state-of the art lung cancer genetic engineered mouse models (some of them unique to our laboratory), lung cancer patient-derived xenografts, as well as clinical samples, our group endeavors to tackle resistance to all these treatments in lung adenocarcinoma by combining the inhibition of oncogen addiction, trough the use of different tyrosine kinase inhibitors, and of non-oncogen addiction, by using the Notch pathway as an example. The major objective is to establish rational combination therapies with the final goal of developing clinical trials at our local hospital, ICM.

Zotero public publish mode


Team

Team Leader  : Antonio Maraver
 

Institut de Recherche en
Cancérologie de Montpellier
Campus Val d’Aurelle
34298 Montpellier cedex 5


 

Tél. : 33 (0)4 67 61 23 95
Fax : 33 (0)4 67 61 37 87
antonio.maraver@inserm.fr

Partners / Funding


© Institut de Recherche en Cancérologie de Montpellier - 2011 - Tous droits réservés - Mentions légales - Connexion - Conception : ID Alizés