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New resistance mechanisms to melanoma targeted therapies : contribution of the translation of RNAs into proteins

Press release | 28 Jul 2014 - 16h31 | By INSERM PRESS OFFICE
Cancer

French investigators have discovered new resistance mechanisms to targeted therapies used for less than three years in the treatment of melanoma. This discovery enables us not only to better understand why these treatments become ineffective but also to reveal new avenues for the management of these aggressive tumours. These studies have been published in the review Nature and have the benefit of an early on-line publication.


The treatment of metastatic melanoma remains a major problem in oncology. Half of the patients suffering from this disorder have a mutation of a protein called BRAF. Medicines targeting this mutated protein, vemurafenib (Zelboraf®) and dabrafenib (Tafinlar), enable the progression of this type of skin cancer to be significantly delayed. Unfortunately, over time, these anti-BRAF compounds loose their efficacy.

Investigators from the Predictive Biomarkers and new molecular strategies in anti-cancer therapy laboratory (Inserm/Gustave Roussy/Paris-Sud University) have shown that the mechanisms used by tumours to resist these treatments involves a protein complex called eIF4F which regulates the synthesis of proteins from RNA. 

 From the biopsies of tumours from patients, investigators also showed that the formation of this complex was diminished in tumours which responded to anti-BRAF and was increased in resistant metastases.

They have also shown that compounds developed by a pharmacochemistry team of the CNRS and by the University of Strasbourg which inhibit the elF4F complex bring about an improvement in the efficacy of vemurafenib in cellular and murine models.

Mélanome

Inserm/Dantchev, Dimitri

These results offer new prospects for the prediction of the efficacy of melanoma treatments using medicines targeting the BRAF protein.

Moreover, over the long term they may result in more effective new treatments emerging to treat not only this fearsome type of cancer, but also certain types of thyroid, colon, lung and brain cancers.

These studies have been conducted by Stéphan Vagner (Inserm U981/Gustave Roussy/Université Paris-Sud, Villejuif; Current address: CNRS UMR3348/Institut Curie, Orsay) and by Caroline Robert (Inserm U981/Gustave Roussy, Dermatology Department/Paris-Sud University, Villejuif) in collaboration with Laurent Désaubry (Therapeutic Innovation Laboratory, CNRS UMR 7200/University of Strasbourg, Illkirch).

The team of Drs Caroline Robert and Stéphan Vagner was supported by PAIR melanoma (Fondation ARC, The league Against Cancer and by INCa), Cancéropôle Ile de France and the group “Ensemble contre le mélanome” (Together against Cancer). This study has also benefited from the support of AAREC Filia Research, from the Wenner-Gren Foundation and from the Swedish Society of Medicine.



TO CITE THIS POST :
Press release – Inserm press room New resistance mechanisms to melanoma targeted therapies : contribution of the translation of RNAs into proteins Link : http://presse.inserm.fr/en/new-resistance-mechanisms-to-melanoma-targeted-therapies-contribution-of-the-translation-of-rnas-into-proteins/14104/
Medias
Researcher Contact

Stephan Vagner
Inserm Unity 981/Gustave Roussy/Université Paris-Sud, Villejuif Current address : CNRS UMR3348/Institut Curie, Orsay
+33 (0)1 42 11 65 10
stephan.vagner@inserm.fr

Press Contact

GUSTAVE ROUSSY : Director of communication– Christine Lascombe
Tél : 01 42 11 41 75 – Mail : christine.lascombe@gustaveroussy.fr

Medial Agency – Claire Parisel
Tél : 01 53 83 81 52 –Mail : claireparisel@medial-rp.com

Sources

eIF4F is a nexus of resistance to anti-BRAF and anti-MEK cancer therapies, Lise Boussemart1,2,3*, Hélène Malka-Mahieu1,2*, Isabelle Girault1*, Delphine Allard1, Oskar Hemmingsson1{, Gorana Tomasic4, Marina Thomas3, Christine Basmadjian5, Nigel Ribeiro5, Fre´de´ric Thuaud5, Christina Mateus3, Emilie Routier3, Nyam Kamsu-Kom1, Sandrine Agoussi1, Alexander M. Eggermont2,3, Laurent De´saubry5, Caroline Robert1,2,3 & Stéphan Vagner1,2,3

1 Inserm UMR981, Villejuif F-94805, France.
2 Université Paris-Sud XI, Kremlin-Biceˆ tre F-94276, France.
3 Gustave Roussy, Dermato-Oncology, Villejuif F-94805, France.
4 Gustave Roussy, PathologyDepartment, Villejuif F-94805, France.
5 CNRS-Strasbourg University, UMR7200, Illkirch F-67400, France. {Present addresses: Department of Surgical and Perioperative Sciences, Umea˚ University, Umea˚SE-90187, Sweden (O.H.); CNRS UMR3348, Institut Curie, Orsay F-91405, France (S.V.).

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