The anti-cancer drug ABTL0812 induces ER stress-mediated cytotoxic autophagy by increasing dihydroceramide levels in cancer cells.

Pau Muñoz-Guardiola,Josefina Casas,Elisabet Megías-Roda,Sònia Solé,Héctor Perez-Montoyo,Marc Yeste-Velasco,Tatiana Erazo,Nora Diéguez-Martínez,Sergio Espinosa-Gil,Cristina Muñoz-Pinedo,Guillermo Yoldi,Jose L Abad,Miguel F Segura,Teresa Moran,Margarita Romeo,Joaquim Bosch-Barrera,Ana Oaknin,Jose Alfón,Carles Domènech,Gemma Fabriàs,Guillermo Velasco & Jose M Lizcano

Phase 1 of ABTL0812, a proautophagic drug, in combination with paclitaxel and carboplatin at first-line in advanced endometrial cancer and squamous cell lung carcinoma

Author(s): Lorena Farinas-Madrid, Purificación Estévez-García, Jose Alejandro Perez-Fidalgo, Joaquim Bosch-Barrera, Teresa Moran, Ernest Nadal, Victor Rodriguez Freixinos, Elisa Calvo, Alejandro Falcon, Paloma Martín-Martorell, Marisol Huerta Alvaro, Maria Pilar Barretina-Ginesta, Margarita Romeo, Marta Gil-Martin, Elena Garralda, Jordi Rodon, Jose M. Lizcano, Carles Domenech, Jose Alberto Alfon, Ana Oaknin; Vall d’Hebron University Hospital Institute of Oncology (VHIO), Barcelona, Spain; Unidad de Tumores Ginecológicos y Genitourinarios, Servicio de Oncologia Médica, Hospital Universitario Virgen del Rocío, Seville, Spain; INCLIVA Research Institute and Hospital Clínico Universitario de Valencia, Valencia, Spain; Institut Catala d'Oncologia, Universitary Hospital Dr. Josep Trueta, Girona, Spain; Institut Català d'Oncologia, Hospital Germans Trias i Pujol, Badalona, Spain; Institut Català d’Oncologia, L’Hospitalet, Barcelona, Spain; Vall d'Hebron Institut of Oncology, Barcelona, Spain; Servicio de Oncologia Médica, Hospital Universitario Virgen del Rocío, Seville, Spain; Medical Oncology Department. Hospital Universitario Virgen del Rocío, Seville, Spain; Hospital Clinic Universitario de Valencia, Valencia, Spain; Oncología Médica, Hospital Universitario de Valencia, Valencia, Spain; Medical Oncology Department, Catalan Institute of Oncology, Girona, Spain; Medical Oncology Department, Institut Català d’Oncologia (ICO) Badalona, B-ARGO, Badalona, Spain; Institut Català d'Oncologia-ICO L’Hospitalet, Barcelona, Spain; Hospital Universitari Vall d’Hebron, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain; Institut de Neurociencies, Universitat Autonoma de Barcelona, Bellaterra, Barcelona, Spain; Ability Pharmaceuticals, Barcelona, Spain; Ability Pharmaceuticals SL, Cerdanyola Del Valles, Spain; Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

Therapeutic potential of the new TRIB3-mediated cell autophagy anticancer drug ABTL0812 in endometrial cancer.

Felip I, Moiola CP, Megino-Luque C, Lopez-Gil C, Cabrera S, Solé-Sánchez S, Muñoz-Guardiola P, Megias-Roda E, Pérez-Montoyo H, Alfon J, Yeste-Velasco M, Santacana M, Dolcet X, Reques A, Oaknin A, Rodríguez-Freixinos V, Lizcano JM, Domènech C, Gil-Moreno A, Matias-Guiu X, Colas E, Eritja N.

Preclinical and clinical development of ABTL0812: a new antitumoral drug that induces autophagy-mediated cancer cell death by upregulating TRIB3 pseudokinase and impairing of Akt/mTORC1 axis.

P. Muñoz-Guardiola, E. Megías-Roda, T. Erazo, H. Pérez, S. Solé-Sánchez, N. Diéguez, M. Yeste, M. Cortal, G. Velasco, J. Alfon, C. Domènech, J.M. Lizcano.

Exploring pharmacokinetic/pharmacodynamic considerations in translational oncology; from preclinical development to Phase II operations

Jose Alfón

Preclinical and clinical development of ABTL0812: a new antitumoral drug that induces autophagy-mediated cancer cell death by upregulating TRIB3 pseudokinase and impairing of Akt/mTORC1 axis.

P. Muñoz-Guardiola, T. Erazo, E. Megías-Roda, H. Pérez-Montoyo, S. Solé-Sánchez, N. Diéguez-Martínez, M. Yeste, M. Cortal, L. Vidal, P. Gascon, M. Gil, M. Romeo, T. Moran, G. Velasco, Jose Alfón, C. Domènech, J.M. Lizcano.

Development of TRIB3 as a novel preclinical and clinical pharmacodynamic biomarker for ABTL0812

H. Pérez-Montoyo, M. Yeste-Velasco, S. Solé-Sánchez, P. Bragado, E. Colàs-Ortega, N. Eritja, A. Lopez-Plana, P. Fernandez-Nogueira, P. Muñoz-Guardiola, E. Megías-Roda, C. Moiola, I. Felip, E. Nadal-Alforja, M. Gil Martin, M. Romeo, T. Moran, A. Gil-Moreno, X. Matias-Guiu, C. Domenech, J.M. Lizcano

The new antitumoral drug ABTL0812 induces autophagic cell death by a dual mechanism: inhibition of Akt/mTORC1 axis and impairing desaturase-1 activity.

Pau Muñoz-Guardiola, Josefina Casas , Elisabet Megías, Nora Diéguez, Mar Lorente, Pedro Rayo, Tatiana Erazo, Sònia Solé-Sánchez, José Alfón, Carles Domènech, Héctor Pérez, Guillermo Velasco, Gemma Fabriàs, Jose M. Lizcano.

Determination of recommended phase II dose of ABTL0812, a novel regulator of Akt/mTOR axis, by pharmacokinetic-pharmacodynamic modelling

J. Alfon L. Vidal L. Gaba I. Victoria M. Gil B. Laquente M. Brunet H. Colom J. Ramis H. Perez-Montoyo M. Cortal M. Gomez-Ferreria P. Muñoz T. Erazo J.M. Lizcano C. Domenech P. Gascon

The New Antitumor Drug ABTL0812 Inhibits the Akt/mTORC1 Axis by Upregulating Tribbles-3 Pseudokinase

Tatiana Erazo, Mar Lorente, Anna López-Plana, Pau Muñoz-Guardiola, Patricia Fernández-Nogueira, José A. García-Martínez, Paloma Bragado, Gemma Fuster, María Salazar, Jordi Espadaler, Javier Hernández-Losa, Jose Ramon Bayascas, Marc Cortal, Laura Vidal, Pedro Gascón, Mariana Gómez-Ferreria, José Alfón, Guillermo Velasco, Carles Domènech and Jose M. Lizcano