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Pharmacological induction of membrane lipid poly-unsaturation sensitizes melanoma to ROS inducers and overcomes acquired resistance to targeted therapy.

Ali TalebiVincent de LaatXander SpotbeenJonas DehairsFlorian RambowAljosja RogiersFrank VanderhoydoncLara RizottoMélanie PlanqueGinevra DoglioniSahar MotamediDavid NittnerTania RoskamsPatrizia AgostinisOliver BechterVeerle BoecxstaensMarjan GarmynMarie O'FarrellAlan WagmanGeorge KembleEleonora LeucciSarah-Maria FendtJean-Christophe MarineJohannes V Swinnen
Published in: Journal of experimental & clinical cancer research : CR (2023)
We conclude that under MAPK inhibition the direct pharmacological inhibition of FASN evokes an exquisite vulnerability to inducers of ROS by increasing membrane lipid poly-unsaturation. The exploitation of this vulnerability by combining MAPK and/or FASN inhibitors with inducers of ROS greatly delays the onset of therapy resistance and increases survival. Our work identifies a clinically actionable combinatorial treatment for therapy-resistant cancer.
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