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1. The PARP1 selective inhibitor saruparib (AZD5305) elicits potent and durable antitumor activity in patient-derived BRCA1/2-associated cancer models

Author

Herencia-Ropero, Andrea, Llop-Guevara, Alba, Staniszewska, Anna D., Domènech-Vivó, Joanna, García-Galea, Eduardo, Moles-Fernández, Alejandro, Pedretti, Flaminia, Domènech, Heura, Rodríguez, Olga, Guzmán, Marta, Arenas, Enrique J., Verdaguer, Helena, Calero-Nieto, Fernando J., Talbot, Sara, Tobalina, Luis, Leo, Elisabetta, Lau, Alan, Nuciforo, Paolo, Dienstmann, Rodrigo, Macarulla, Teresa, Arribas, Joaquín, Díez, Orland, Gutiérrez-Enríquez, Sara, Forment, Josep V., O’Connor, Mark J., Albertella, Mark, Balmaña, Judith, and Serra, Violeta

Published
2024
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2. Generation of Metastatic Cholangiocarcinoma Patient-Derived Xenograft Models

Author

Yáñez-Bartolomé, Mariana, primary, Serra-Camprubí, Queralt, additional, Arenas, Enrique J., additional, Escorihuela, Marta, additional, Castet, Florian, additional, Fabregat-Franco, Carles, additional, Querol, Jessica, additional, Arribas, Joaquín, additional, Peiró, Sandra, additional, Macarulla, Teresa, additional, and Tian, Tian V., additional

Published
2024
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6. Figure S3 from Early-Stage Breast Cancer Detection in Breast Milk

Author

Saura, Cristina, primary, Ortiz, Carolina, primary, Matito, Judit, primary, Arenas, Enrique J., primary, Suñol, Anna, primary, Martín, Ágatha, primary, Córdoba, Octavi, primary, Martínez-Sabadell, Alex, primary, García-Ruiz, Itziar, primary, Miranda, Ignacio, primary, Morales-Comas, Clara, primary, Carrasco, Estela, primary, Viaplana, Cristina, primary, Peg, Vicente, primary, Nuciforo, Paolo, primary, Bayó-Puxan, Neus, primary, Gonzalez-Medina, Alberto, primary, Miquel, Josep M., primary, Gómez-Rey, Marina, primary, Villacampa, Guillermo, primary, Arévalo, Silvia, primary, Espinosa-Bravo, Martín, primary, Balmaña, Judith, primary, Dienstmann, Rodrigo, primary, Arribas, Joaquin, primary, Tabernero, Josep, primary, Vivancos, Ana, primary, and Sansó, Miriam, primary

Published
2023
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7. Data from Early-Stage Breast Cancer Detection in Breast Milk

Author

Saura, Cristina, primary, Ortiz, Carolina, primary, Matito, Judit, primary, Arenas, Enrique J., primary, Suñol, Anna, primary, Martín, Ágatha, primary, Córdoba, Octavi, primary, Martínez-Sabadell, Alex, primary, García-Ruiz, Itziar, primary, Miranda, Ignacio, primary, Morales-Comas, Clara, primary, Carrasco, Estela, primary, Viaplana, Cristina, primary, Peg, Vicente, primary, Nuciforo, Paolo, primary, Bayó-Puxan, Neus, primary, Gonzalez-Medina, Alberto, primary, Miquel, Josep M., primary, Gómez-Rey, Marina, primary, Villacampa, Guillermo, primary, Arévalo, Silvia, primary, Espinosa-Bravo, Martín, primary, Balmaña, Judith, primary, Dienstmann, Rodrigo, primary, Arribas, Joaquin, primary, Tabernero, Josep, primary, Vivancos, Ana, primary, and Sansó, Miriam, primary

Published
2023
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8. Early-Stage Breast Cancer Detection in Breast Milk

Author

Saura, Cristina, primary, Ortiz, Carolina, additional, Matito, Judit, additional, Arenas, Enrique J., additional, Suñol, Anna, additional, Martín, Ágatha, additional, Córdoba, Octavi, additional, Martínez-Sabadell, Alex, additional, García-Ruiz, Itziar, additional, Miranda, Ignacio, additional, Morales-Comas, Clara, additional, Carrasco, Estela, additional, Viaplana, Cristina, additional, Peg, Vicente, additional, Nuciforo, Paolo, additional, Bayó-Puxan, Neus, additional, Gonzalez-Medina, Alberto, additional, Miquel, Josep M., additional, Gómez-Rey, Marina, additional, Villacampa, Guillermo, additional, Arévalo, Silvia, additional, Espinosa-Bravo, Martín, additional, Balmaña, Judith, additional, Dienstmann, Rodrigo, additional, Arribas, Joaquin, additional, Tabernero, Josep, additional, Vivancos, Ana, additional, and Sansó, Miriam, additional

Published
2023
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9. Data from Human Metastatic Cholangiocarcinoma Patient-Derived Xenografts and Tumoroids for Preclinical Drug Evaluation

Author

Serra-Camprubí, Queralt, primary, Verdaguer, Helena, primary, Oliveros, Winona, primary, Lupión-Garcia, Núria, primary, Llop-Guevara, Alba, primary, Molina, Cristina, primary, Vila-Casadesús, Maria, primary, Turpin, Anthony, primary, Neuzillet, Cindy, primary, Frigola, Joan, primary, Querol, Jessica, primary, Yáñez-Bartolomé, Mariana, primary, Castet, Florian, primary, Fabregat-Franco, Carles, primary, Escudero-Iriarte, Carmen, primary, Escorihuela, Marta, primary, Arenas, Enrique J., primary, Bernadó-Morales, Cristina, primary, Haro, Noemí, primary, Giles, Francis J., primary, Pozo, Óscar J., primary, Miquel, Josep M., primary, Nuciforo, Paolo G., primary, Vivancos, Ana, primary, Melé, Marta, primary, Serra, Violeta, primary, Arribas, Joaquín, primary, Tabernero, Josep, primary, Peiró, Sandra, primary, Macarulla, Teresa, primary, and Tian, Tian V., primary

Published
2023
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10. Supplementary Table S1 from Human Metastatic Cholangiocarcinoma Patient-Derived Xenografts and Tumoroids for Preclinical Drug Evaluation

Author

Serra-Camprubí, Queralt, primary, Verdaguer, Helena, primary, Oliveros, Winona, primary, Lupión-Garcia, Núria, primary, Llop-Guevara, Alba, primary, Molina, Cristina, primary, Vila-Casadesús, Maria, primary, Turpin, Anthony, primary, Neuzillet, Cindy, primary, Frigola, Joan, primary, Querol, Jessica, primary, Yáñez-Bartolomé, Mariana, primary, Castet, Florian, primary, Fabregat-Franco, Carles, primary, Escudero-Iriarte, Carmen, primary, Escorihuela, Marta, primary, Arenas, Enrique J., primary, Bernadó-Morales, Cristina, primary, Haro, Noemí, primary, Giles, Francis J., primary, Pozo, Óscar J., primary, Miquel, Josep M., primary, Nuciforo, Paolo G., primary, Vivancos, Ana, primary, Melé, Marta, primary, Serra, Violeta, primary, Arribas, Joaquín, primary, Tabernero, Josep, primary, Peiró, Sandra, primary, Macarulla, Teresa, primary, and Tian, Tian V., primary

Published
2023
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11. Supplementary Figure S6 from Human Metastatic Cholangiocarcinoma Patient-Derived Xenografts and Tumoroids for Preclinical Drug Evaluation

Author

Serra-Camprubí, Queralt, primary, Verdaguer, Helena, primary, Oliveros, Winona, primary, Lupión-Garcia, Núria, primary, Llop-Guevara, Alba, primary, Molina, Cristina, primary, Vila-Casadesús, Maria, primary, Turpin, Anthony, primary, Neuzillet, Cindy, primary, Frigola, Joan, primary, Querol, Jessica, primary, Yáñez-Bartolomé, Mariana, primary, Castet, Florian, primary, Fabregat-Franco, Carles, primary, Escudero-Iriarte, Carmen, primary, Escorihuela, Marta, primary, Arenas, Enrique J., primary, Bernadó-Morales, Cristina, primary, Haro, Noemí, primary, Giles, Francis J., primary, Pozo, Óscar J., primary, Miquel, Josep M., primary, Nuciforo, Paolo G., primary, Vivancos, Ana, primary, Melé, Marta, primary, Serra, Violeta, primary, Arribas, Joaquín, primary, Tabernero, Josep, primary, Peiró, Sandra, primary, Macarulla, Teresa, primary, and Tian, Tian V., primary

Published
2023
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13. Data from Preclinical In Vivo Validation of the RAD51 Test for Identification of Homologous Recombination-Deficient Tumors and Patient Stratification

Author

Pellegrino, Benedetta, primary, Herencia-Ropero, Andrea, primary, Llop-Guevara, Alba, primary, Pedretti, Flaminia, primary, Moles-Fernández, Alejandro, primary, Viaplana, Cristina, primary, Villacampa, Guillermo, primary, Guzmán, Marta, primary, Rodríguez, Olga, primary, Grueso, Judit, primary, Jiménez, Jose, primary, Arenas, Enrique J., primary, Degasperi, Andrea, primary, Dias, João M.L., primary, Forment, Josep V., primary, O'Connor, Mark J., primary, Déas, Olivier, primary, Cairo, Stefano, primary, Zhou, Yinghui, primary, Musolino, Antonino, primary, Caldas, Carlos, primary, Nik-Zainal, Serena, primary, Clarke, Robert B., primary, Nuciforo, Paolo, primary, Díez, Orland, primary, Serres-Créixams, Xavier, primary, Peg, Vicente, primary, Espinosa-Bravo, Martín, primary, Macarulla, Teresa, primary, Oaknin, Ana, primary, Mateo, Joaquin, primary, Arribas, Joaquín, primary, Dienstmann, Rodrigo, primary, Bellet, Meritxell, primary, Oliveira, Mafalda, primary, Saura, Cristina, primary, Gutiérrez-Enríquez, Sara, primary, Balmaña, Judith, primary, and Serra, Violeta, primary

Published
2023
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14. Supplementary Table from Preclinical In Vivo Validation of the RAD51 Test for Identification of Homologous Recombination-Deficient Tumors and Patient Stratification

Author

Pellegrino, Benedetta, primary, Herencia-Ropero, Andrea, primary, Llop-Guevara, Alba, primary, Pedretti, Flaminia, primary, Moles-Fernández, Alejandro, primary, Viaplana, Cristina, primary, Villacampa, Guillermo, primary, Guzmán, Marta, primary, Rodríguez, Olga, primary, Grueso, Judit, primary, Jiménez, Jose, primary, Arenas, Enrique J., primary, Degasperi, Andrea, primary, Dias, João M.L., primary, Forment, Josep V., primary, O'Connor, Mark J., primary, Déas, Olivier, primary, Cairo, Stefano, primary, Zhou, Yinghui, primary, Musolino, Antonino, primary, Caldas, Carlos, primary, Nik-Zainal, Serena, primary, Clarke, Robert B., primary, Nuciforo, Paolo, primary, Díez, Orland, primary, Serres-Créixams, Xavier, primary, Peg, Vicente, primary, Espinosa-Bravo, Martín, primary, Macarulla, Teresa, primary, Oaknin, Ana, primary, Mateo, Joaquin, primary, Arribas, Joaquín, primary, Dienstmann, Rodrigo, primary, Bellet, Meritxell, primary, Oliveira, Mafalda, primary, Saura, Cristina, primary, Gutiérrez-Enríquez, Sara, primary, Balmaña, Judith, primary, and Serra, Violeta, primary

Published
2023
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15. Supplementary Figure from Preclinical In Vivo Validation of the RAD51 Test for Identification of Homologous Recombination-Deficient Tumors and Patient Stratification

Author

Pellegrino, Benedetta, primary, Herencia-Ropero, Andrea, primary, Llop-Guevara, Alba, primary, Pedretti, Flaminia, primary, Moles-Fernández, Alejandro, primary, Viaplana, Cristina, primary, Villacampa, Guillermo, primary, Guzmán, Marta, primary, Rodríguez, Olga, primary, Grueso, Judit, primary, Jiménez, Jose, primary, Arenas, Enrique J., primary, Degasperi, Andrea, primary, Dias, João M.L., primary, Forment, Josep V., primary, O'Connor, Mark J., primary, Déas, Olivier, primary, Cairo, Stefano, primary, Zhou, Yinghui, primary, Musolino, Antonino, primary, Caldas, Carlos, primary, Nik-Zainal, Serena, primary, Clarke, Robert B., primary, Nuciforo, Paolo, primary, Díez, Orland, primary, Serres-Créixams, Xavier, primary, Peg, Vicente, primary, Espinosa-Bravo, Martín, primary, Macarulla, Teresa, primary, Oaknin, Ana, primary, Mateo, Joaquin, primary, Arribas, Joaquín, primary, Dienstmann, Rodrigo, primary, Bellet, Meritxell, primary, Oliveira, Mafalda, primary, Saura, Cristina, primary, Gutiérrez-Enríquez, Sara, primary, Balmaña, Judith, primary, and Serra, Violeta, primary

Published
2023
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17. MSK1 regulates luminal cell differentiation and metastatic dormancy in ER+ breast cancer

Author

Gawrzak, Sylwia, Rinaldi, Lorenzo, Gregorio, Sara, Arenas, Enrique J., Salvador, Fernando, Urosevic, Jelena, Figueras-Puig, Cristina, Rojo, Federico, del Barco Barrantes, Ivan, Cejalvo, Juan Miguel, Palafox, Marta, Guiu, Marc, Berenguer-Llergo, Antonio, Symeonidi, Aikaterini, Bellmunt, Anna, Kalafatovic, Daniela, Arnal-Estapé, Anna, Fernández, Esther, Müllauer, Barbara, Groeneveld, Rianne, Slobodnyuk, Konstantin, Stephan-Otto Attolini, Camille, Saura, Cristina, Arribas, Joaquín, Cortes, Javier, Rovira, Ana, Muñoz, Montse, Lluch, Ana, Serra, Violeta, Albanell, Joan, Prat, Aleix, Nebreda, Angel R., Benitah, Salvador Aznar, and Gomis, Roger R.

Published
2018
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18. Therapy-Induced Senescence Enhances the Efficacy of HER2-Targeted Antibody–Drug Conjugates in Breast Cancer

Author

Duro-Sánchez, Santiago, Nadal-Serrano, Mercedes, Lalinde-Gutiérrez, Marta., Arenas, Enrique J, Bernadó Morales, Cristina, Morancho, Beatriz, Escorihuela, Marta, Pérez-Ramos, Sandra, Escrivá-de-Romaní, Santiago, Gandullo-Sánchez, Lucía, Pandiella, Atanasio, Esteve-Codina, Anna, Rodilla, Verónica, Dijcks, Fred .A., Dokter, Wim .H.A., Cortés, Javier, Saura, Cristina, Arribas, Joaquín V, Universitat Autònoma de Barcelona, Institut Català de la Salut, [Duro-Sánchez S, Lalinde-Gutiérrez M] Preclinical and Translational Research Program, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Centro de Investigacion Biomédica en Red de Cáncer (CIBERONC), Barcelona, Spain. Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra, Spain. Cancer Research Program, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain. [Nadal-Serrano M, Arenas EJ, Bernadó Morales C, Morancho B] Preclinical and Translational Research Program, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Centro de Investigacion Biomédica en Red de Cáncer (CIBERONC), Barcelona, Spain. [Escorihuela M, Pérez-Ramos S, Rodilla V, Cortés J] Preclinical and Translational Research Program, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Escrivá-de-Romaní S] Breast Cancer and Melanoma Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Gandullo-Sánchez L] Centro de Investigacion Biomédica en Red de Cáncer (CIBERONC), Barcelona, Spain. Breast Cancer and Melanoma Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Saura C] Cancer Research Program, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain. [Arribas J] Preclinical and Translational Research Program, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Centro de Investigacion Biomédica en Red de Cáncer (CIBERONC), Barcelona, Spain. Cancer Research Program, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain. Universitat Pompeu Fabra (UPF), Barcelona, Spain. Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus, American Breast Cancer Foundation, Instituto de Salud Carlos III, Fundación Mutua Madrileña, and Asociación Española Contra el Cáncer

Subjects
Cancer Research, Immunoconjugates, Receptor, ErbB-2, Neoplasms::Neoplasms by Site::Breast Neoplasms [DISEASES], Mama--Càncer--Aspectes genètics, Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], Antineoplastic Agents, Breast Neoplasms, Other subheadings::Other subheadings::/drug therapy [Other subheadings], Cathepsin B, Medicaments antineoplàstics, Mama--Tumors, Cell Line, Tumor, Humans, Animals, Other subheadings::/therapeutic use [Other subheadings], Mama--Càncer--Tractament, neoplasias::neoplasias por localización::neoplasias de la mama [ENFERMEDADES], Anticossos monoclonals - Ús terapèutic, Otros calificadores::/uso terapéutico [Otros calificadores], Chemical Actions and Uses::Toxic Actions::Noxae::Immunoconjugates [CHEMICALS AND DRUGS], acciones y usos químicos::acciones tóxicas::noxas::inmunoconjugados [COMPUESTOS QUÍMICOS Y DROGAS], Trastuzumab, Xenograft Model Antitumor Assays, Oncology, Mama - Càncer - Tractament, Female
Abstract

Antibody–drug conjugates (ADC) are antineoplastic agents recently introduced into the antitumor arsenal. T-DM1, a trastuzumab-based ADC that relies on lysosomal processing to release the payload, is approved for HER2-positive breast cancer. Next-generation ADCs targeting HER2, such as [vic-]trastuzumab duocarmazine (SYD985), bear linkers cleavable by lysosomal proteases and membrane-permeable drugs, mediating a bystander effect by which neighboring antigen-negative cells are eliminated. Many antitumor therapies, like DNA-damaging agents or CDK4/6 inhibitors, can induce senescence, a cellular state characterized by stable cell-cycle arrest. Another hallmark of cellular senescence is the enlargement of the lysosomal compartment. Given the relevance of the lysosome to the mechanism of action of ADCs, we hypothesized that therapies that induce senescence would potentiate the efficacy of HER2-targeting ADCs. Treatment with the DNA-damaging agent doxorubicin and CDK4/6 inhibitor induced lysosomal enlargement and senescence in several breast cancer cell lines. While senescence-inducing drugs did not increase the cytotoxic effect of ADCs on target cells, the bystander effect was enhanced when HER2-negative cells were cocultured with HER2-low cells. Knockdown experiments demonstrated the importance of cathepsin B in the enhanced bystander effect, suggesting that cathepsin B mediates linker cleavage. In breast cancer patient-derived xenografts, a combination treatment of CDK4/6 inhibitor and SYD985 showed improved antitumor effects over either treatment alone. These data support the strategy of combining next-generation ADCs targeting HER2 with senescence-inducing therapies for tumors with heterogenous and low HER2 expression., This work was supported by Breast Cancer Research Foundation (BCRF-20-008), Instituto de Salud Carlos III (project reference numbers AC15/00062, CB16/12/00449 and PI19/01181), the EC under the framework of the ERA-NET TRANSCAN-2 initiative co-financed by FEDER, Fundacion Mutua Madrilena and Asociación ~ Española Contra el Cáncer. S. Duro-Sanchez is supported by the Spanish Ministerio de Universidades by the grant Formacion de Profesorado Universitario (FPU20/05388). A. Esteve-Codina is funded by ISCIII /MINECO (PT17/0009/0019) and co-funded by FEDER.

Published
2022

20. Human Metastatic Cholangiocarcinoma Patient-Derived Xenografts and Tumoroids for Preclinical Drug Evaluation

Author

Serra-Camprubí, Queralt, primary, Verdaguer, Helena, additional, Oliveros, Winona, additional, Lupión-Garcia, Núria, additional, Llop-Guevara, Alba, additional, Molina, Cristina, additional, Vila-Casadesús, Maria, additional, Turpin, Anthony, additional, Neuzillet, Cindy, additional, Frigola, Joan, additional, Querol, Jessica, additional, Yáñez-Bartolomé, Mariana, additional, Castet, Florian, additional, Fabregat-Franco, Carles, additional, Escudero-Iriarte, Carmen, additional, Escorihuela, Marta, additional, Arenas, Enrique J., additional, Bernadó-Morales, Cristina, additional, Haro, Noemí, additional, Giles, Francis J., additional, Pozo, Óscar J., additional, Miquel, Josep M., additional, Nuciforo, Paolo G., additional, Vivancos, Ana, additional, Melé, Marta, additional, Serra, Violeta, additional, Arribas, Joaquín, additional, Tabernero, Josep, additional, Peiró, Sandra, additional, Macarulla, Teresa, additional, and Tian, Tian V., additional

Published
2022
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21. Abstract 3970: Acquired cancer cell resistance to T cell bispecific antibodies and CAR T targeting HER2 through JAK2 down-modulation

Author

Martínez-Sabadell, Alex, primary, Arenas, Enrique J., additional, Ruiz, Irene Rius, additional, Alonso, Macarena Román, additional, Escorihuela, Marta, additional, Luque, Antonio, additional, Fajardo, Carlos Alberto, additional, Gros, Alena, additional, Klein, Christian, additional, and Arribas, Joaquin, additional

Published
2022
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22. Targeting HER2-AXL heterodimerization to overcome resistance to HER2 blockade in breast cancer

Author

Adam-Artigues, Anna, primary, Arenas, Enrique J., additional, Martínez-Sabadell, Alex, additional, Brasó-Maristany, Fara, additional, Cervera, Raimundo, additional, Tormo, Eduardo, additional, Hernando, Cristina, additional, Martínez, María Teresa, additional, Carbonell-Asins, Juan, additional, Simón, Soraya, additional, Poveda, Jesús, additional, Moragón, Santiago, additional, Zazo, Sandra, additional, Martínez, Débora, additional, Rovira, Ana, additional, Burgués, Octavio, additional, Rojo, Federico, additional, Albanell, Joan, additional, Bermejo, Begoña, additional, Lluch, Ana, additional, Prat, Aleix, additional, Arribas, Joaquín, additional, Eroles, Pilar, additional, and Cejalvo, Juan Miguel, additional

Published
2022
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24. Preclinical In Vivo Validation of the RAD51 Test for Identification of Homologous Recombination-Deficient Tumors and Patient Stratification

Author

Pellegrino, Benedetta, primary, Herencia-Ropero, Andrea, additional, Llop-Guevara, Alba, additional, Pedretti, Flaminia, additional, Moles-Fernández, Alejandro, additional, Viaplana, Cristina, additional, Villacampa, Guillermo, additional, Guzmán, Marta, additional, Rodríguez, Olga, additional, Grueso, Judit, additional, Jiménez, Jose, additional, Arenas, Enrique J., additional, Degasperi, Andrea, additional, Dias, João M.L., additional, Forment, Josep V., additional, O'Connor, Mark J., additional, Déas, Olivier, additional, Cairo, Stefano, additional, Zhou, Yinghui, additional, Musolino, Antonino, additional, Caldas, Carlos, additional, Nik-Zainal, Serena, additional, Clarke, Robert B., additional, Nuciforo, Paolo, additional, Díez, Orland, additional, Serres-Créixams, Xavier, additional, Peg, Vicente, additional, Espinosa-Bravo, Martín, additional, Macarulla, Teresa, additional, Oaknin, Ana, additional, Mateo, Joaquin, additional, Arribas, Joaquín, additional, Dienstmann, Rodrigo, additional, Bellet, Meritxell, additional, Oliveira, Mafalda, additional, Saura, Cristina, additional, Gutiérrez-Enríquez, Sara, additional, Balmaña, Judith, additional, and Serra, Violeta, additional

Published
2022
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25. Publisher Correction: MSK1 regulates luminal cell differentiation and metastatic dormancy in ER+ breast cancer

Author

Gawrzak, Sylwia, Rinaldi, Lorenzo, Gregorio, Sara, Arenas, Enrique J., Salvador, Fernando, Urosevic, Jelena, Figueras-Puig, Cristina, Rojo, Federico, del Barco Barrantes, Ivan, Cejalvo, Juan Miguel, Palafox, Marta, Guiu, Marc, Berenguer-Llergo, Antonio, Symeonidi, Aikaterini, Bellmunt, Anna, Kalafatovic, Daniela, Arnal-Estapé, Anna, Fernández, Esther, Müllauer, Barbara, Groeneveld, Rianne, Slobodnyuk, Konstantin, Stephan-Otto Attolini, Camille, Saura, Cristina, Arribas, Joaquín, Cortes, Javier, Rovira, Ana, Muñoz, Montse, Lluch, Ana, Serra, Violeta, Albanell, Joan, Prat, Aleix, Nebreda, Angel R., Benitah, Salvador Aznar, and Gomis, Roger R.

Published
2018
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31. p95HER2–T cell bispecific antibody for breast cancer treatment

Author

Rius Ruiz, Irene, primary, Vicario, Rocio, additional, Morancho, Beatriz, additional, Morales, Cristina Bernadó, additional, Arenas, Enrique J., additional, Herter, Sylvia, additional, Freimoser-Grundschober, Anne, additional, Somandin, Jitka, additional, Sam, Johannes, additional, Ast, Oliver, additional, Barriocanal, Águeda Martinez, additional, Luque, Antonio, additional, Escorihuela, Marta, additional, Varela, Ismael, additional, Cuartas, Isabel, additional, Nuciforo, Paolo, additional, Fasani, Roberta, additional, Peg, Vicente, additional, Rubio, Isabel, additional, Cortés, Javier, additional, Serra, Violeta, additional, Escriva-de-Romani, Santiago, additional, Sperinde, Jeff, additional, Chenna, Ahmed, additional, Huang, Weidong, additional, Winslow, John, additional, Albanell, Joan, additional, Seoane, Joan, additional, Scaltriti, Maurizio, additional, Baselga, Jose, additional, Tabernero, Josep, additional, Umana, Pablo, additional, Bacac, Marina, additional, Saura, Cristina, additional, Klein, Christian, additional, and Arribas, Joaquín, additional

Published
2018
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32. FoxA and LIPG endothelial lipase control the uptake of extracellular lipids for breast cancer growth

Author

Slebe, Felipe, primary, Rojo, Federico, additional, Vinaixa, Maria, additional, García-Rocha, Mar, additional, Testoni, Giorgia, additional, Guiu, Marc, additional, Planet, Evarist, additional, Samino, Sara, additional, Arenas, Enrique J., additional, Beltran, Antoni, additional, Rovira, Ana, additional, Lluch, Ana, additional, Salvatella, Xavier, additional, Yanes, Oscar, additional, Albanell, Joan, additional, Guinovart, Joan J., additional, and Gomis, Roger R., additional

Published
2016
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33. RARRES3 suppresses breast cancer lung metastasis by regulating adhesion and differentiation

Author

Bioquímica y biología molecular, Biokimika eta biologia molekularra, Morales, Mónica, Arenas, Enrique J., Urosevic, Jelena, Guiu, Marc, Fernández, Esther, Planet, Evarist, Fenwick, Robert Bryn, Fernández-Ruiz, Sonia, Salvatella, Xavier, Reverter, David, Carracedo Pérez, Arkaitz, Massagué, Joan, Gomis, Roger R, Bioquímica y biología molecular, Biokimika eta biologia molekularra, Morales, Mónica, Arenas, Enrique J., Urosevic, Jelena, Guiu, Marc, Fernández, Esther, Planet, Evarist, Fenwick, Robert Bryn, Fernández-Ruiz, Sonia, Salvatella, Xavier, Reverter, David, Carracedo Pérez, Arkaitz, Massagué, Joan, and Gomis, Roger R

Abstract

In estrogen receptor-negative breast cancer patients, metastatic relapse usually occurs in the lung and is responsible for the fatal outcome of the disease. Thus, a better understanding of the biology of metastasis is needed. In particular, biomarkers to identify patients that are at risk of lung metastasis could open the avenue for new therapeutic opportunities. Here we characterize the biological activity of RARRES3, a new metastasis suppressor gene whose reduced expression in the primary breast tumors identifies a subgroup of patients more likely to develop lung metastasis. We show that RARRES3 downregulation engages metastasis-initiating capabilities by facilitating adhesion of the tumor cells to the lung parenchyma. In addition, impaired tumor cell differentiation due to the loss of RARRES3 phospholipase A1/A2 activity also contributes to lung metastasis. Our results establish RARRES3 downregulation as a potential biomarker to identify patients at high risk of lung metastasis who might benefit from a differentiation treatment in the adjuvant programme.

Published
2014

34. RARRES 3suppresses breast cancer lung metastasis by regulating adhesion and differentiation

Author

Morales, Mònica, primary, Arenas, Enrique J, additional, Urosevic, Jelena, additional, Guiu, Marc, additional, Fernández, Esther, additional, Planet, Evarist, additional, Fenwick, Robert Bryn, additional, Fernández‐Ruiz, Sonia, additional, Salvatella, Xavier, additional, Reverter, David, additional, Carracedo, Arkaitz, additional, Massagué, Joan, additional, and Gomis, Roger R, additional

Published
2014
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35. Generation of Metastatic Cholangiocarcinoma Patient-Derived Xenograft Models.

Author

Yáñez-Bartolomé M, Serra-Camprubí Q, Arenas EJ, Escorihuela M, Castet F, Fabregat-Franco C, Querol J, Arribas J, Peiró S, Macarulla T, and Tian TV

Subjects
Humans, Animals, Mice, Disease Models, Animal, Cholangiocarcinoma pathology, Cholangiocarcinoma genetics, Bile Duct Neoplasms pathology, Bile Duct Neoplasms genetics, Xenograft Model Antitumor Assays methods
Abstract

Cholangiocarcinoma (CCA) poses a substantial clinical hurdle as it is often detected at advanced metastatic stages with limited therapeutic options. To enhance our understanding of advanced CCA, it is imperative to establish preclinical models that faithfully recapitulate the disease's characteristics. Patient-derived xenograft (PDX) models have emerged as a valuable approach in cancer research, offering an avenue to reproduce and study the genomic, histologic, and molecular features of the original human tumors. By faithfully preserving the heterogeneity, microenvironmental interactions, and drug responses observed in human tumors, PDX models serve as highly relevant and predictive preclinical tools. Here, we present a comprehensive protocol that outlines the step-by-step process of generating and maintaining PDX models using biopsy samples from patients with advanced metastatic CCA. The protocol encompasses crucial aspects such as tissue processing, xenograft transplantation, and subsequent monitoring of the PDX models. By employing this protocol, we aim to establish a robust collection of PDX models that accurately reflect the genomic landscape, histologic diversity, and therapeutic responses observed in advanced CCA, thereby enabling improved translational research, drug development, and personalized treatment strategies for patients facing this challenging disease., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Published
2024
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36. Human Metastatic Cholangiocarcinoma Patient-Derived Xenografts and Tumoroids for Preclinical Drug Evaluation.

Author

Serra-Camprubí Q, Verdaguer H, Oliveros W, Lupión-Garcia N, Llop-Guevara A, Molina C, Vila-Casadesús M, Turpin A, Neuzillet C, Frigola J, Querol J, Yáñez-Bartolomé M, Castet F, Fabregat-Franco C, Escudero-Iriarte C, Escorihuela M, Arenas EJ, Bernadó-Morales C, Haro N, Giles FJ, Pozo ÓJ, Miquel JM, Nuciforo PG, Vivancos A, Melé M, Serra V, Arribas J, Tabernero J, Peiró S, Macarulla T, and Tian TV

Subjects
Humans, Drug Evaluation, Preclinical, Heterografts, Poly(ADP-ribose) Polymerase Inhibitors pharmacology, Bile Ducts, Intrahepatic, Cholangiocarcinoma drug therapy, Cholangiocarcinoma genetics, Bile Duct Neoplasms drug therapy, Bile Duct Neoplasms genetics
Abstract

Purpose: Cholangiocarcinoma (CCA) is usually diagnosed at advanced stages, with limited therapeutic options. Preclinical models focused on unresectable metastatic CCA are necessary to develop rational treatments. Pathogenic mutations in IDH1/2, ARID1A/B, BAP1, and BRCA1/2 have been identified in 30%-50% of patients with CCA. Several types of tumor cells harboring these mutations exhibit homologous recombination deficiency (HRD) phenotype with enhanced sensitivity to PARP inhibitors (PARPi). However, PARPi treatment has not yet been tested for effectiveness in patient-derived models of advanced CCA., Experimental Design: We have established a collection of patient-derived xenografts from patients with unresectable metastatic CCA (CCA_PDX). The CCA_PDXs were characterized at both histopathologic and genomic levels. We optimized a protocol to generate CCA tumoroids from CCA_PDXs. We tested the effects of PARPis in both CCA tumoroids and CCA_PDXs. Finally, we used the RAD51 assay to evaluate the HRD status of CCA tissues., Results: This collection of CCA_PDXs recapitulates the histopathologic and molecular features of their original tumors. PARPi treatments inhibited the growth of CCA tumoroids and CCA_PDXs with pathogenic mutations of BRCA2, but not those with mutations of IDH1, ARID1A, or BAP1. In line with these findings, only CCA_PDX and CCA patient biopsy samples with mutations of BRCA2 showed RAD51 scores compatible with HRD., Conclusions: Our results suggest that patients with advanced CCA with pathogenic mutations of BRCA2, but not those with mutations of IDH1, ARID1A, or BAP1, are likely to benefit from PARPi therapy. This collection of CCA_PDXs provides new opportunities for evaluating drug response and prioritizing clinical trials., (©2022 The Authors; Published by the American Association for Cancer Research.)

Published
2023
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37. IFNγ Signaling in Natural and Therapy-Induced Antitumor Responses.

Author

Martínez-Sabadell A, Arenas EJ, and Arribas J

Subjects
Cell Proliferation, Cytokines therapeutic use, Humans, Immunity, Interferon-gamma, Neoplasms drug therapy
Abstract

IFNγ is a cytokine produced by a restricted number of immune cells that acts on every nucleated cell type. Consistent with this remarkably wide spectrum of targets, the effects of IFNγ are highly pleiotropic. On cells of the immune system, IFNγ signaling has generally a pro-inflammatory effect, coordinating the innate and adaptive responses. On nonimmune cells, IFNγ tends to exert the opposite effect; it inhibits cell proliferation, induces cell death, and, in addition, promotes their recognition by the immune system. These effects on the immune and nonimmune compartments play a crucial role during the immunoediting of tumors and, as shown by recent reports, also determine the efficacy of certain immunotherapies. Different therapeutic interventions to target IFNγ signaling are currently under way, and the emerging picture indicates that rewiring IFNγ signaling, disrupted in some cancer cells, may be an efficacious antitumor therapeutic strategy., (©2021 American Association for Cancer Research.)

Published
2022
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38. Mammary cancer stem cells reinitiation assessment at the metastatic niche: the lung and bone.

Author

Guiu M, Arenas EJ, Gawrzak S, Pavlovic M, and Gomis RR

Subjects
Animals, Bone Neoplasms diagnosis, Bone Neoplasms pathology, Bone Neoplasms secondary, Cell Culture Techniques, Disease Models, Animal, Female, Flow Cytometry, Humans, Luminescent Measurements methods, Lung Neoplasms diagnosis, Lung Neoplasms pathology, Lung Neoplasms secondary, Mice, Molecular Imaging methods, Tumor Cells, Cultured, Breast Neoplasms pathology, Neoplastic Stem Cells metabolism, Neoplastic Stem Cells pathology, Tumor Microenvironment
Abstract

Mammary cancer stem cells (MCSC) have been operationally defined as cells that re-form secondary tumors upon transplantation into immunodeficient mice. Building on this observation, it has also been suggested that MCSCs are responsible for metastasis as well as evasion and resistance to therapeutic treatments. MCSC reinitiating potential is usually tested by implantation of limited amounts of cells orthotopically or subcutaneously, yet this poorly recapitulates the metastatic niche where truly metastatic reinitiation will occur. Herein, we describe the implantation of small amounts of MCSC selected populations in the bone (intra tibiae injection) and the lung (intra thoracic injection) to test for their metastatic reinitiation capabilities.

Published
2015
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