Santamaría Martínez, Enrique

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Santamaría Martínez

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Enrique

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Ciencias de la Salud

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Now showing 1 - 2 of 2
  • PublicationOpen Access
    Signature-driven repurposing of Midostaurin for combination with MEK1/2 and KRASG12C inhibitors in lung cancer
    (Springer Nature, 2023) Macaya, Irati; Roman, Marta; Welch, Connor; Entrialgo-Cadierno, Rodrigo; Salmon, Marina; Santos, Alba; Feliu, Iker; Kovalski, Joanna; López Erdozain, Inés; Rodríguez-Remírez, María; Palomino Echeverría, Sara; Lonfgren, Shane M.; Ferrero, Macarena; Calabuig, Silvia; Ludwig, Iziar A.; Lara-Astiaso, David; Jantus-Lewintre, Eloisa; Guruceaga, Elizabeth; Narayanan, Shruthi; Ponz Sarvisé, Mariano; Pineda Lucena, Antonio; Lecanda, Fernando; Ruggero, Davide; Khatri, Purvesh; Santamaría Martínez, Enrique; Fernández Irigoyen, Joaquín; Ferrer, Irene; Paz-Ares, Luis; Drosten, Matthias; Barbacid, Mariano; Gil-Bazo, Ignacio; Vicent, Silvestre; Ciencias de la Salud; Osasun Zientziak
    Drug combinations are key to circumvent resistance mechanisms compromising response to single anti-cancer targeted therapies. The implementation of combinatorial approaches involving MEK1/2 or KRASG12C inhibitors in the context of KRAS-mutated lung cancers focuses fundamentally on targeting KRAS proximal activators or effectors. However, the antitumor effect is highly determined by compensatory mechanisms arising in defined cell types or tumor subgroups. A potential strategy to find drug combinations targeting a larger fraction of KRAS-mutated lung cancers may capitalize on the common, distal gene expression output elicited by oncogenic KRAS. By integrating a signature-driven drug repurposing approach with a pairwise pharmacological screen, here we show synergistic drug combinations consisting of multi-tyrosine kinase PKC inhibitors together with MEK1/2 or KRASG12C inhibitors. Such combinations elicit a cytotoxic response in both in vitro and in vivo models, which in part involves inhibition of the PKC inhibitor target AURKB. Proteome profiling links dysregulation of MYC expression to the effect of both PKC inhibitor-based drug combinations. Furthermore, MYC overexpression appears as a resistance mechanism to MEK1/2 and KRASG12C inhibitors. Our study provides a rational framework for selecting drugs entering combinatorial strategies and unveils MEK1/2- and KRASG12C-based therapies for lung cancer.
  • PublicationOpen Access
    Influence of short-term training on functional capacity and (anti-)inflammatory immune signalling in acute hospitalization
    (Wiley, 2020) Ramírez Vélez, Robinson; Martínez Velilla, Nicolás; Fernández Irigoyen, Joaquín; Santamaría Martínez, Enrique; Izquierdo Redín, Mikel; Palomino Echeverría, Sara; Ciencias de la Salud; Osasun Zientziak; Universidad Pública de Navarra / Nafarroako Unibertsitate Publikoa; Gobierno de Navarra / Nafarroako Gobernua
    To investigate the infuence of exercise on inflammatory signalling, it was performed cytokine array profiling in human serum to identify inflammatory cytokines produced after a 3 day in-hospital intervention including individualized moderate-intensity resistance, balance, and walking exercises vs. medical usual-care for acute hospitalization in very elderly patients.