Oncogenic pathways in lung cancer : A. Maraver


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 preclinical 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.



Xiong H, Mancini M, Gobert M, Shen S, Furtado G, Lira S, Parkhurst C, Brengues M, Tadokoro C, Trimarchi T, Singh A, Khiabanian H, Minuzzo S, Indraccolo S, Lobry C, Aifantis I, Herranz D, Lafaille J, Maraver A Spleen plays a major role in DLL4-driven acute T-cell lymphoblastic leukemia. Theranostics. 2021;11(4):1594-1608. doi:10.7150/thno.48067

Bousquet Mur E, Bernardo S, Papon L, Mancini M, Fabbrizio E, Goussard M, Ferrer I, Giry A, Quantin X, Pujol J-L, Calvayrac O, Moll H, Glasson Y, Pirot N, Turtoi A, Cañamero M, Wong K-K, Yarden Y, Casanova E, Soria J-C, Colinge J, Siebel C, Favre G, Paz-Ares L, Maraver A Notch inhibition overcomes resistance to tyrosine kinase inhibitors in EGFR-driven lung adenocarcinoma. J Clin Invest. 2020;130(2):612-624. doi:10.1172/JCI126896

Mancini M, Gaborit N, Mazzeo L, Romaniello D, Salame T, Lindzen M, Mahlknecht G, Enuka Y, Burton D, Roth L, Noronha A, Marrocco I, Adreka D, Altstadter R, 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. 2018;10(2):294-308. doi:10.15252/emmm.201708076

Rivera-Torres J, Guzman-Martinez G, Villa-Bellosta R, Orbe J, Gonzalez-Gomez C, Serrano M, Diez J, Andres V, Maraver A Targeting gamma-secretases protect against angiotensin II-induced cardiac hypertrophy. Journal of hypertension. 2015;33. doi:10.1097/HJH.0000000000000463

Maraver A, Fernandez-Marcos P, Cash T, Mendez-Pertuz M, Duenas M, Maietta P, Martinelli P, Munoz-Martin M, Martinez-Fernandez M, Canamero M, Roncador G, Martinez-Torrecuadrada J, Grivas D, de la Pompa J, Valencia A, Paramio J, Real F, Serrano M NOTCH pathway inactivation promotes bladder cancer progression. The Journal of clinical investigation. 2015;125. doi:10.1172/JCI78185

Fernandez-Marcos P, Serrano M, Maraver A Bladder cancer and the Notch pathway. Oncotarget. 2015;6.

Maraver A, Fernández-Marcos P, Herranz D, Muñoz-Martin M, Gomez-Lopez G, Cañamero M, Mulero F, Megías D, Sanchez-Carbayo M, Shen J, Sanchez-Cespedes M, Palomero T, Ferrando A, Serrano M Therapeutic effect of ?-secretase inhibition in KrasG12V-driven non-small cell lung carcinoma by derepression of DUSP1 and inhibition of ERK. Cancer Cell. 2012;22(2):222-234. doi:10.1016/j.ccr.2012.06.014


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

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