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2. Development and Independent Validation of a Prognostic Gene Expression Signature Based on RB1, PTEN, and TP53 in Metastatic Hormone-sensitive Prostate Cancer Patients

Author

Jiménez, Natalia, Garcia de Herreros, Marta, Reig, Òscar, Marín-Aguilera, Mercedes, Aversa, Caterina, Ferrer-Mileo, Laura, García-Esteve, Samuel, Rodríguez-Carunchio, Leonardo, Trias, Isabel, Font, Albert, Rodriguez-Vida, Alejo, Climent, Miguel Ángel, Cros, Sara, Chirivella, Isabel, Domènech, Montserrat, Figols, Mariona, Carles, Joan, Suárez, Cristina, Herrero Rivera, Daniel, González-Billalabeitia, Enrique, Cívico, Claudia, Sala-González, Núria, Ruiz de Porras, Vicenç, Ribal, Maria J., Prat, Aleix, and Mellado, Begoña

Published
2024
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3. Prospective Assessment of Bone Metabolism Biomarkers and Survival in Metastatic Castration-resistant Prostate Cancer Patients Treated with Radium-223: The PRORADIUM Study

Author

Romero-Laorden, Nuria, Lorente, David, de Velasco, Guillermo, Lozano, Rebeca, Herrera, Bernardo, Puente, Javier, López, Pedro P., Medina, Ana, Almagro, Elena, Gonzalez-Billalabeitia, Enrique, Villla-Guzman, Jose Carlos, González-del-Alba, Aránzazu, Borrega, Pablo, Laínez, Nuria, Fernández-Freire, Ana, Hernández, Amaia, Rodriguez-Vida, Alejo, Chirivella, Isabel, Fernandez-Parra, Eva, López-Campos, Fernando, Isabel Pacheco, Maria, Morales-Barrera, Rafael, Fernández, Ovidio, Villatoro, Rosa, Luque, Raquel, Hernando, Susana, Castellano, Daniel C., Castro, Elena, and Olmos, David

Published
2024
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4. A predictive model for hospitalization and survival to COVID-19 in a retrospective population-based study

Author

Alejandro Cisterna-García, Antonio Guillén-Teruel, Marcos Caracena, Enrique Pérez, Fernando Jiménez, Francisco J. Francisco-Verdú, Gabriel Reina, Enrique González-Billalabeitia, José Palma, Álvaro Sánchez-Ferrer, and Juan A. Botía

Subjects
Medicine, Science
Abstract

Abstract The development of tools that provide early triage of COVID-19 patients with minimal use of diagnostic tests, based on easily accessible data, can be of vital importance in reducing COVID-19 mortality rates during high-incidence scenarios. This work proposes a machine learning model to predict mortality and risk of hospitalization using both 2 simple demographic features and 19 comorbidities obtained from 86,867 electronic medical records of COVID-19 patients, and a new method (LR-IPIP) designed to deal with data imbalance problems. The model was able to predict with high accuracy (90–93%, ROC-AUC = 0.94) the patient's final status (deceased or discharged), while its accuracy was medium (71–73%, ROC-AUC = 0.75) with respect to the risk of hospitalization. The most relevant characteristics for these models were age, sex, number of comorbidities, osteoarthritis, obesity, depression, and renal failure. Finally, to facilitate its use by clinicians, a user-friendly website has been developed ( https://alejandrocisterna.shinyapps.io/PROVIA ).

Published
2022
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6. The transcriptional landscape of metastatic hormone-naive prostate cancer

Author

Martin-Martin, Natalia, primary, Garcia-Longarte, Saioa, additional, Corres-Mendizabal, Jon, additional, Lazcano, Uxue, additional, Astobiza, Ianire, additional, Bozal-Basterra, Laura, additional, Herranz, Nicolas, additional, van Splunder, Hielke, additional, Carlevaris, Onintza, additional, Pujana-Vaquerizo, Mikel, additional, Blasco, María Teresa, additional, Aransay, Ana M., additional, Rosino, Antonio, additional, Tudela, Julian, additional, Jimenez, Daniel, additional, Martinez, Alberto, additional, Salca, Andrei, additional, Santos-Martín, Aida, additional, Rey, Sofía, additional, Ugalde-Olano, Aitziber, additional, Gonzalo, David, additional, Graupera, Mariona, additional, Gomis, Roger R., additional, Mateo, Joaquin, additional, Unda, Miguel, additional, Gonzalez-Billalabeitia, Enrique, additional, Loizaga-Iriarte, Ana, additional, Mendizabal, Isabel, additional, and Carracedo, Arkaitz, additional

Published
2024
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8. Large retroperitoneal lymphadenopathy and increased risk of venous thromboembolism in patients receiving first‐line chemotherapy for metastatic germ cell tumors: A study by the global germ cell cancer group (G3)

Author

Ben Tran, Jose M. Ruiz‐Morales, Enrique Gonzalez‐Billalabeitia, Anna Patrikidou, Eitan Amir, Christoph Seidel, Carsten Bokemeyer, Christian Fankhauser, Thomas Hermanns, Alexey Rumyantsev, Alexey Tryakin, Margarida Brito, Aude Fléchon, Edmond Michael Kwan, Tina Cheng, Daniel Castellano, Xavier Garcia del Muro, Anis A. Hamid, Margaret Ottaviano, Giovannella Palmieri, Robert Kitson, Alison Reid, Daniel Y. C. Heng, and Philippe L. Bedard

Subjects
deep vein thrombosis, germ cell tumor, pulmonary embolism, testicular cancer, vascular access device, venous thromboembolism, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Metastatic germ cell tumor (mGCT) patients receiving chemotherapy have increased risk of life‐threatening venous thromboembolism (VTE). Identifying VTE risk factors may guide thromboprophylaxis in this highly curable population. Methods Data were collected from mGCT patients receiving first‐line platinum‐based chemotherapy at 22 centers. Predefined variables included International Germ Cell Cancer Collaborative Group (IGCCCG) risk classification, long‐axis diameter of largest retroperitoneal lymph node (RPLN), Khorana score, and use of indwelling vascular access device (VAD). VTE occurring at baseline, during chemotherapy and within 90 days, was analyzed. Results Data from 1135 patients were collected. Median age was 31 years (range 10‐74). IGCCCG risk was 64% good, 20% intermediate, and 16% poor. VTE occurred in 150 (13%) patients. RPLN >3.5 cm demonstrated highest discriminatory accuracy for VTE (AUC 0.632, P

Published
2020
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9. Plasma tumour DNA as an early indicator of treatment response in metastatic castration-resistant prostate cancer

Author

Conteduca, Vincenza, Wetterskog, Daniel, Scarpi, Emanuela, Romanel, Alessandro, Gurioli, Giorgia, Jayaram, Anuradha, Lolli, Cristian, Tandefelt, Delila Gasi, Schepisi, Giuseppe, Casadei, Chiara, Wingate, Anna, Matteucci, Federica, Paganelli, Giovanni, Gonzalez-Billalabeitia, Enrique, Demichelis, Francesca, De Giorgi, Ugo, and Attard, Gerhardt

Published
2020
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10. Prospective Assessment of Bone Metabolism Biomarkers and Survival in Metastatic Castration-resistant Prostate Cancer Patients Treated with Radium-223: The PRORADIUM Study

Author

Romero-Laorden, Nuria, primary, Lorente, David, additional, de Velasco, Guillermo, additional, Lozano, Rebeca, additional, Herrera, Bernardo, additional, Puente, Javier, additional, López, Pedro P., additional, Medina, Ana, additional, Almagro, Elena, additional, Gonzalez-Billalabeitia, Enrique, additional, Villla-Guzman, Jose Carlos, additional, González-del-Alba, Aránzazu, additional, Borrega, Pablo, additional, Laínez, Nuria, additional, Fernández-Freire, Ana, additional, Hernández, Amaia, additional, Rodriguez-Vida, Alejo, additional, Chirivella, Isabel, additional, Fernandez-Parra, Eva, additional, López-Campos, Fernando, additional, Isabel Pacheco, Maria, additional, Morales-Barrera, Rafael, additional, Fernández, Ovidio, additional, Villatoro, Rosa, additional, Luque, Raquel, additional, Hernando, Susana, additional, Castellano, Daniel C., additional, Castro, Elena, additional, and Olmos, David, additional

Published
2023
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11. PTEN self-regulates through USP11 via the PI3K-FOXO pathway to stabilize tumor suppression

Author

Mi Kyung Park, Yixin Yao, Weiya Xia, Stephanie Rebecca Setijono, Jae Hwan Kim, Isabelle K. Vila, Hui-Hsuan Chiu, Yun Wu, Enrique González Billalabeitia, Min Gyu Lee, Robert G. Kalb, Mien-Chie Hung, Pier Paolo Pandolfi, Su Jung Song, and Min Sup Song

Subjects
Science
Abstract

PTEN is a lipid phosphatase that functions as a dose-dependent tumor suppressor through the PI3K/AKT pathway. Here the authors describe a signaling feedback mechanism where PTEN stability is regulated through transcriptional upregulation of X-linked ubiquitin-specific protease 11 (USP11) via the PI3K/FOXO pathway.

Published
2019
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14. A correlative biomarker study and integrative prognostic model in chemotherapy‐naïve metastatic castration‐resistant prostate cancer treated with enzalutamide

Author

María P. Fernandez‐Perez, Enrique Perez‐Navarro, Teresa Alonso‐Gordoa, Vicenza Conteduca, Albert Font, Sergio Vázquez‐Estévez, Aránzazu González‐del‐Alba, Daniel Wetterskog, Emmanuel S. Antonarakis, Begona Mellado, Ovidio Fernandez‐Calvo, María J. Méndez‐Vidal, Miguel A. Climent, Ignacio Duran, Enrique Gallardo, Angel Rodriguez Sanchez, Carmen Santander, Maria I. Sáez, Javier Puente, Julian Tudela, Alberto Martínez, Maria J. López‐Andreo, José Padilla, Rebeca Lozano, David Hervas, Jun Luo, Ugo de Giorgi, Daniel Castellano, Gerhardt Attard, Enrique Grande, and Enrique Gonzalez‐Billalabeitia

Subjects
Oncology, Medicina, Urology, Oncología
Abstract

Background There is a considerable need to incorporate biomarkers of resistance to new antiandrogen agents in the management of castration-resistant prostate cancer (CRPC). Methods We conducted a phase II trial of enzalutamide in first-line chemo-naïve asymptomatic or minimally symptomatic mCRPC and analyzed the prognostic value of TMPRSS2-ERG and other biomarkers, including circulating tumor cells (CTCs), androgen receptor splice variant (AR-V7) in CTCs and plasma Androgen Receptor copy number gain (AR-gain). These biomarkers were correlated with treatment response and survival outcomes and developed a clinical–molecular prognostic model using penalized cox-proportional hazard model. This model was validated in an independent cohort. Results Ninety-eight patients were included. TMPRSS2-ERG fusion gene was detected in 32 patients with no differences observed in efficacy outcomes. CTC detection was associated with worse outcome and AR-V7 in CTCs was associated with increased rate of progression as best response. Plasma AR gain was strongly associated with an adverse outcome, with worse median prostate specific antigen (PSA)-PFS (4.2 vs. 14.7 m; p

Published
2022

15. Expert recommendations on the management of patients with metastatic castration-resistant prostate cancer who progress after CHAARTED or LATITUDE

Author

Javier Puente, Urbano Anido, Miguel Ángel Climent, Enrique Gonzalez-Billalabeitia, Nuria Lainez, Julio Lambea, José Pablo Maroto, Maria Jose Mendez-Vidal, Álvaro Montesa, Angel Rodriguez, Curro Zambrana, and Aránzazu González-del-Alba

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Objective: Our aim was to provide practical recommendations on the management of patients with metastatic castration-resistant prostate cancer (mCRPC) who have progressed after docetaxel plus androgen-deprivation therapy (ADT) or abiraterone plus ADT. Methods: Systematic literature review (SLR), nominal group meeting, and Delphi process. A panel of 12 experts was established who defined the scope, users, and sections of the document. We performed an SLR in order to assess the efficacy and safety of available drugs in patients with mCRPC. Abstracts from the American Society of Oncology and European Society for Medical Oncology meetings were also examined. The results were discussed during an expert meeting in which 14 recommendations were generated. The level of agreement with the recommendations was also tested by 13 additional experts following the Delphi process. Recommendations were voted by means of scores ranging from 0 (total disagreement) to 10 (total agreement). We defined agreement when at least 70% of the experts voted ⩾7. Next, we assigned a level of evidence and grade to the recommendation using the Oxford Centre for Evidence-based Medicine Levels of Evidence, following which the final document was drafted. Results: The literature search did not find any articles meeting the inclusion criteria. Finally, 13 out of 14 recommendations were accepted after two Delphi rounds (two were modified after the first round). They pertain to general and individual case-based treatment recommendations. Conclusions: In mCRPC patients who have progressed after docetaxel or abiraterone plus ADT in the metastatic hormone-sensitive prostate cancer setting, these recommendations may support treatment decision-making, due to the lack of evidence or other globally accepted sequencing algorithms.

Published
2020
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16. Recent advances in genitourinary tumors: A review focused on biology and systemic treatment

Author

González del Alba, Aránzazu, Arranz, José Ángel, Puente, Javier, Méndez-Vidal, María José, Gallardo, Enrique, Grande, Enrique, Pérez-Valderrama, Begoña, González-Billalabeitia, Enrique, Lázaro-Quintela, Martín, Pinto, Álvaro, Lainez, Nuria, Piulats, Josep M., Esteban, Emilio, Maroto Rey, José Pablo, García, Jorge A., and Suárez, Cristina

Published
2017
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17. Consensus Recommendations from the Spanish Germ Cell Cancer Group on the Use of High-dose Chemotherapy in Germ Cell Cancer

Author

González-Billalabeitia, Enrique, Sepúlveda, Juan Manuel, Maroto, Pablo, Aparicio, Jorge, Arranz, Jose Angel, Esteban, Emilio, Gironés, Regina, López-Brea, Marta, Mendez-Vidal, María José, Pinto, Alvaro, Sastre, Javier, de Prado, Diego Soto, Terrasa, Josefa, Vázquez, Sergio, Powles, Thomas, Beyer, Jörg, Castellano, Daniel, and del Muro, Xavier García

Published
2017
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18. Peapod FOS trial: A phase 2 clinical trial of pembrolizumab in combination with carboplatin and cabazitaxel in aggressive variant metastatic castration-resistant prostate cancer.

Author

Esteban Villarrubia, Jorge, Alonso Gordoa, Teresa, Mellado-González, Begoña, Duran, Ignacio, Pinto, Alvaro, Sanchez, Alfredo, Font Pous, Albert, Vazquez-Estevez, Sergio, Puente, Javier, Grande, Enrique, Climent, Miguel Ángel, Maroto-Rey, Pablo, Perez-Gracia, Jose Luis, Ponce Aix, Santiago, Castellano, Daniel, and Gonzalez-Billalabeitia, Enrique

Published
2024
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19. Molecular profiling and clinical relevance of low PTEN expression in patients with metastatic hormone-sensitive prostate cancer.

Author

Garcia de Herreros, Marta, Jiménez, Natalia, Reig Torras, Oscar, Ruiz de Porras, Vicente, Pardo, Juan Carlos, Font Pous, Albert, Aversa, Caterina, Ferrer-Mileo, Laura, Mazariegos, Manuel, Rodriguez-Carunchio, Leonardo, Trias, Isabel, Jordà, Mireia, García-Esteve, Samuel, Cros Costa, Sara, Fernandez-Mañas, Laia, Figols, Mariona, Gonzalez-Billalabeitia, Enrique, Chirivella, Isabel, Rodriguez-Vida, Alejo, and Mellado-Gonzalez, Begoña

Published
2024
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20. Coformulation of pembrolizumab and vibostolimab in patients (pts) with docetaxel-pretreated metastatic castration-resistant prostate cancer (mCRPC): KEYNOTE-365 cohort G.

Author

Fong, Peter C.C., Kwiatkowski, Mariusz, Mosca, Alessandra, Perez Valderrama, Begona, Huang, Yi-Hsiu, Zedan, Ahmed H., Kuc, Kamil, Wiechno, Pawel, Laguerre, Brigitte, Gonzalez-Billalabeitia, Enrique, Osipov, Mikhail, Sener Dede, Didem, Goh, Jeffrey, Daugaard, Gedske, Zhu, Pengfei, Imai, Kentaro, liu, yingjie, and Arranz Arija, Jose Angel

Published
2024
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21. Pembrolizumab (pembro) plus lenvatinib (lenva) in patients (pts) with docetaxel-pretreated, metastatic castration-resistant prostate cancer (mCRPC): KEYNOTE-365 cohort E.

Author

Augustin, Marinela, Laguerre, Brigitte, Baldini, Capucine, Zedan, Ahmed H., Gonzalez-Billalabeitia, Enrique, Fong, Peter C.C., Zukov, Ruslan, Hammerer, Peter, Prentice, Mark, Shore, Neal D., Necchi, Andrea, Todenhöfer, Tilman, Kessler, Elizabeth R., Köse, Fatih, Gurney, Howard, Perez Valderrama, Begona, Zhu, Pengfei, Imai, Kentaro, liu, yingjie, and McDermott, Raymond S.

Published
2024
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23. An aberrant SREBP-dependent lipogenic program promotes metastatic prostate cancer

Author

Chen, Ming, Zhang, Jiangwen, Sampieri, Katia, Clohessy, John G., Mendez, Lourdes, Gonzalez-Billalabeitia, Enrique, Liu, Xue-Song, Lee, Yu-Ru, Fung, Jacqueline, Katon, Jesse M., Menon, Archita Venugopal, Webster, Kaitlyn A., Ng, Christopher, Palumbieri, Maria Dilia, Diolombi, Moussa S., Breitkopf, Susanne B., Teruya-Feldstein, Julie, Signoretti, Sabina, Bronson, Roderick T., Asara, John M., Castillo-Martin, Mireia, Cordon-Cardo, Carlos, and Pandolfi, Pier Paolo

Published
2018
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24. Supplementary Figure 1 from Vulnerabilities of PTEN–TP53-Deficient Prostate Cancers to Compound PARP–PI3K Inhibition

Author

González-Billalabeitia, Enrique, primary, Seitzer, Nina, primary, Song, Su Jung, primary, Song, Min Sup, primary, Patnaik, Akash, primary, Liu, Xue-Song, primary, Epping, Mirjam T., primary, Papa, Antonella, primary, Hobbs, Robin M., primary, Chen, Ming, primary, Lunardi, Andrea, primary, Ng, Christopher, primary, Webster, Kaitlyn A., primary, Signoretti, Sabina, primary, Loda, Massimo, primary, Asara, John M., primary, Nardella, Caterina, primary, Clohessy, John G., primary, Cantley, Lewis C., primary, and Pandolfi, Pier Paolo, primary

Published
2023
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25. Supplementary Figure 5 from Vulnerabilities of PTEN–TP53-Deficient Prostate Cancers to Compound PARP–PI3K Inhibition

Author

González-Billalabeitia, Enrique, primary, Seitzer, Nina, primary, Song, Su Jung, primary, Song, Min Sup, primary, Patnaik, Akash, primary, Liu, Xue-Song, primary, Epping, Mirjam T., primary, Papa, Antonella, primary, Hobbs, Robin M., primary, Chen, Ming, primary, Lunardi, Andrea, primary, Ng, Christopher, primary, Webster, Kaitlyn A., primary, Signoretti, Sabina, primary, Loda, Massimo, primary, Asara, John M., primary, Nardella, Caterina, primary, Clohessy, John G., primary, Cantley, Lewis C., primary, and Pandolfi, Pier Paolo, primary

Published
2023
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26. Supplementary Figure 2 from Vulnerabilities of PTEN–TP53-Deficient Prostate Cancers to Compound PARP–PI3K Inhibition

Author

González-Billalabeitia, Enrique, primary, Seitzer, Nina, primary, Song, Su Jung, primary, Song, Min Sup, primary, Patnaik, Akash, primary, Liu, Xue-Song, primary, Epping, Mirjam T., primary, Papa, Antonella, primary, Hobbs, Robin M., primary, Chen, Ming, primary, Lunardi, Andrea, primary, Ng, Christopher, primary, Webster, Kaitlyn A., primary, Signoretti, Sabina, primary, Loda, Massimo, primary, Asara, John M., primary, Nardella, Caterina, primary, Clohessy, John G., primary, Cantley, Lewis C., primary, and Pandolfi, Pier Paolo, primary

Published
2023
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27. Supplementary Materials and Methods, Figure Legends from Vulnerabilities of PTEN–TP53-Deficient Prostate Cancers to Compound PARP–PI3K Inhibition

Author

González-Billalabeitia, Enrique, primary, Seitzer, Nina, primary, Song, Su Jung, primary, Song, Min Sup, primary, Patnaik, Akash, primary, Liu, Xue-Song, primary, Epping, Mirjam T., primary, Papa, Antonella, primary, Hobbs, Robin M., primary, Chen, Ming, primary, Lunardi, Andrea, primary, Ng, Christopher, primary, Webster, Kaitlyn A., primary, Signoretti, Sabina, primary, Loda, Massimo, primary, Asara, John M., primary, Nardella, Caterina, primary, Clohessy, John G., primary, Cantley, Lewis C., primary, and Pandolfi, Pier Paolo, primary

Published
2023
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28. Data from Vulnerabilities of PTEN–TP53-Deficient Prostate Cancers to Compound PARP–PI3K Inhibition

Author

González-Billalabeitia, Enrique, primary, Seitzer, Nina, primary, Song, Su Jung, primary, Song, Min Sup, primary, Patnaik, Akash, primary, Liu, Xue-Song, primary, Epping, Mirjam T., primary, Papa, Antonella, primary, Hobbs, Robin M., primary, Chen, Ming, primary, Lunardi, Andrea, primary, Ng, Christopher, primary, Webster, Kaitlyn A., primary, Signoretti, Sabina, primary, Loda, Massimo, primary, Asara, John M., primary, Nardella, Caterina, primary, Clohessy, John G., primary, Cantley, Lewis C., primary, and Pandolfi, Pier Paolo, primary

Published
2023
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29. Supplementary Figure 3 from Vulnerabilities of PTEN–TP53-Deficient Prostate Cancers to Compound PARP–PI3K Inhibition

Author

González-Billalabeitia, Enrique, primary, Seitzer, Nina, primary, Song, Su Jung, primary, Song, Min Sup, primary, Patnaik, Akash, primary, Liu, Xue-Song, primary, Epping, Mirjam T., primary, Papa, Antonella, primary, Hobbs, Robin M., primary, Chen, Ming, primary, Lunardi, Andrea, primary, Ng, Christopher, primary, Webster, Kaitlyn A., primary, Signoretti, Sabina, primary, Loda, Massimo, primary, Asara, John M., primary, Nardella, Caterina, primary, Clohessy, John G., primary, Cantley, Lewis C., primary, and Pandolfi, Pier Paolo, primary

Published
2023
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30. Supplementary Figure 6 from Vulnerabilities of PTEN–TP53-Deficient Prostate Cancers to Compound PARP–PI3K Inhibition

Author

González-Billalabeitia, Enrique, primary, Seitzer, Nina, primary, Song, Su Jung, primary, Song, Min Sup, primary, Patnaik, Akash, primary, Liu, Xue-Song, primary, Epping, Mirjam T., primary, Papa, Antonella, primary, Hobbs, Robin M., primary, Chen, Ming, primary, Lunardi, Andrea, primary, Ng, Christopher, primary, Webster, Kaitlyn A., primary, Signoretti, Sabina, primary, Loda, Massimo, primary, Asara, John M., primary, Nardella, Caterina, primary, Clohessy, John G., primary, Cantley, Lewis C., primary, and Pandolfi, Pier Paolo, primary

Published
2023
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31. Supplementary Figure 4 from Vulnerabilities of PTEN–TP53-Deficient Prostate Cancers to Compound PARP–PI3K Inhibition

Author

González-Billalabeitia, Enrique, primary, Seitzer, Nina, primary, Song, Su Jung, primary, Song, Min Sup, primary, Patnaik, Akash, primary, Liu, Xue-Song, primary, Epping, Mirjam T., primary, Papa, Antonella, primary, Hobbs, Robin M., primary, Chen, Ming, primary, Lunardi, Andrea, primary, Ng, Christopher, primary, Webster, Kaitlyn A., primary, Signoretti, Sabina, primary, Loda, Massimo, primary, Asara, John M., primary, Nardella, Caterina, primary, Clohessy, John G., primary, Cantley, Lewis C., primary, and Pandolfi, Pier Paolo, primary

Published
2023
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32. Supplementary Figure 7 from Vulnerabilities of PTEN–TP53-Deficient Prostate Cancers to Compound PARP–PI3K Inhibition

Author

González-Billalabeitia, Enrique, primary, Seitzer, Nina, primary, Song, Su Jung, primary, Song, Min Sup, primary, Patnaik, Akash, primary, Liu, Xue-Song, primary, Epping, Mirjam T., primary, Papa, Antonella, primary, Hobbs, Robin M., primary, Chen, Ming, primary, Lunardi, Andrea, primary, Ng, Christopher, primary, Webster, Kaitlyn A., primary, Signoretti, Sabina, primary, Loda, Massimo, primary, Asara, John M., primary, Nardella, Caterina, primary, Clohessy, John G., primary, Cantley, Lewis C., primary, and Pandolfi, Pier Paolo, primary

Published
2023
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33. A correlative biomarker study and integrative prognostic model in chemotherapy‐naïve metastatic castration‐resistant prostate cancer treated with enzalutamide

Author

Fernández Perez, María P., Pérez Navarro, Enrique, Alonso Gordoa, Teresa, Conteduca, Vicenza, Font, Albert, Vázquez Estévez, Sergio, González del Alba, Aránzazu, Wetterskog, Daniel, Antonarakis, Emmanuel S., Mellado, Begona, Fernández Calvo, Ovidio, Méndez Vidal, María J., Climent, Miguel A., Duran, Ignacio, Gallardo, Enrique, Rodriguez Sánchez, Angel, Santander, Carmen, Sáez, Maria I., Puente, Javier de la, Tudela, Julian, Martínez, Alberto, López Andreo, Maria J., Padilla, José, Lozano, Rebeca, Hervas, David, Luo, Jun, de Giorgi, Ugo, Castellano, Daniel, Attard, Gerhardt, Grande, Enrique, Gónzalez Billalabeitia, Enrique, Fernández Perez, María P., Pérez Navarro, Enrique, Alonso Gordoa, Teresa, Conteduca, Vicenza, Font, Albert, Vázquez Estévez, Sergio, González del Alba, Aránzazu, Wetterskog, Daniel, Antonarakis, Emmanuel S., Mellado, Begona, Fernández Calvo, Ovidio, Méndez Vidal, María J., Climent, Miguel A., Duran, Ignacio, Gallardo, Enrique, Rodriguez Sánchez, Angel, Santander, Carmen, Sáez, Maria I., Puente, Javier de la, Tudela, Julian, Martínez, Alberto, López Andreo, Maria J., Padilla, José, Lozano, Rebeca, Hervas, David, Luo, Jun, de Giorgi, Ugo, Castellano, Daniel, Attard, Gerhardt, Grande, Enrique, and Gónzalez Billalabeitia, Enrique

Abstract

CRUE-CSIC (Acuerdos Transformativos 2022), Background There is a considerable need to incorporate biomarkers of resistance to new antiandrogen agents in the management of castration-resistant prostate cancer (CRPC). Methods We conducted a phase II trial of enzalutamide in first-line chemo-naïve asymptomatic or minimally symptomatic mCRPC and analyzed the prognostic value of TMPRSS2-ERG and other biomarkers, including circulating tumor cells (CTCs), androgen receptor splice variant (AR-V7) in CTCs and plasma Androgen Receptor copy number gain (AR-gain). These biomarkers were correlated with treatment response and survival outcomes and developed a clinical–molecular prognostic model using penalized cox-proportional hazard model. This model was validated in an independent cohort. Results Ninety-eight patients were included. TMPRSS2-ERG fusion gene was detected in 32 patients with no differences observed in efficacy outcomes. CTC detection was associated with worse outcome and AR-V7 in CTCs was associated with increased rate of progression as best response. Plasma AR gain was strongly associated with an adverse outcome, with worse median prostate specific antigen (PSA)-PFS (4.2 vs. 14.7 m; p < 0.0001), rad-PFS (4.5 vs. 27.6 m; p < 0.0001), and OS (12.7 vs. 38.1 m; p < 0.0001). The clinical prognostic model developed in PREVAIL was validated (C-Index 0.70) and the addition of plasma AR (C-Index 0.79; p < 0.001) increased its prognostic ability. We generated a parsimonious model including alkaline phosphatase (ALP); PSA and AR gain (C-index 0.78) that was validated in an independent cohort. Conclusions TMPRSS2-ERG detection did not correlate with differential activity of enzalutamide in first-line mCRPC. However, we observed that CTCs and plasma AR gain were the most relevant biomarkers., Instituto de Salud Carlos III (ISCIII), Depto. de Medicina, Fac. de Medicina, TRUE, pub

Published
2023

34. Supplementary Figure 3 from Vulnerabilities of PTEN–TP53-Deficient Prostate Cancers to Compound PARP–PI3K Inhibition

Author

Pier Paolo Pandolfi, Lewis C. Cantley, John G. Clohessy, Caterina Nardella, John M. Asara, Massimo Loda, Sabina Signoretti, Kaitlyn A. Webster, Christopher Ng, Andrea Lunardi, Ming Chen, Robin M. Hobbs, Antonella Papa, Mirjam T. Epping, Xue-Song Liu, Akash Patnaik, Min Sup Song, Su Jung Song, Nina Seitzer, and Enrique González-Billalabeitia

Abstract

PDF - 14407K, Supporting histology for Olaparib treatment in vivo.

Published
2023

35. Supplementary Figure 5 from Vulnerabilities of PTEN–TP53-Deficient Prostate Cancers to Compound PARP–PI3K Inhibition

Author

Pier Paolo Pandolfi, Lewis C. Cantley, John G. Clohessy, Caterina Nardella, John M. Asara, Massimo Loda, Sabina Signoretti, Kaitlyn A. Webster, Christopher Ng, Andrea Lunardi, Ming Chen, Robin M. Hobbs, Antonella Papa, Mirjam T. Epping, Xue-Song Liu, Akash Patnaik, Min Sup Song, Su Jung Song, Nina Seitzer, and Enrique González-Billalabeitia

Abstract

PDF - 632K, Preclinical assessment of Olaparib and BKM120 treatment in vivo.

Published
2023

36. Supplementary Figure 1 from Vulnerabilities of PTEN–TP53-Deficient Prostate Cancers to Compound PARP–PI3K Inhibition

Author

Pier Paolo Pandolfi, Lewis C. Cantley, John G. Clohessy, Caterina Nardella, John M. Asara, Massimo Loda, Sabina Signoretti, Kaitlyn A. Webster, Christopher Ng, Andrea Lunardi, Ming Chen, Robin M. Hobbs, Antonella Papa, Mirjam T. Epping, Xue-Song Liu, Akash Patnaik, Min Sup Song, Su Jung Song, Nina Seitzer, and Enrique González-Billalabeitia

Abstract

PDF - 546K, Olaparib induces a differing response in vitro depending on the genetic background.

Published
2023

37. Supplementary Figure 2 from Vulnerabilities of PTEN–TP53-Deficient Prostate Cancers to Compound PARP–PI3K Inhibition

Author

Pier Paolo Pandolfi, Lewis C. Cantley, John G. Clohessy, Caterina Nardella, John M. Asara, Massimo Loda, Sabina Signoretti, Kaitlyn A. Webster, Christopher Ng, Andrea Lunardi, Ming Chen, Robin M. Hobbs, Antonella Papa, Mirjam T. Epping, Xue-Song Liu, Akash Patnaik, Min Sup Song, Su Jung Song, Nina Seitzer, and Enrique González-Billalabeitia

Abstract

PDF - 2951K, Olaparib induces a differing response in vivo depending on the genetic background.

Published
2023

38. Supplementary Figure 4 from Vulnerabilities of PTEN–TP53-Deficient Prostate Cancers to Compound PARP–PI3K Inhibition

Author

Pier Paolo Pandolfi, Lewis C. Cantley, John G. Clohessy, Caterina Nardella, John M. Asara, Massimo Loda, Sabina Signoretti, Kaitlyn A. Webster, Christopher Ng, Andrea Lunardi, Ming Chen, Robin M. Hobbs, Antonella Papa, Mirjam T. Epping, Xue-Song Liu, Akash Patnaik, Min Sup Song, Su Jung Song, Nina Seitzer, and Enrique González-Billalabeitia

Abstract

PDF - 114k, Supporting western blot analysis and drug treatment in prostate cancer cell lines.

Published
2023

39. Supplementary Materials and Methods, Figure Legends from Vulnerabilities of PTEN–TP53-Deficient Prostate Cancers to Compound PARP–PI3K Inhibition

Author

Pier Paolo Pandolfi, Lewis C. Cantley, John G. Clohessy, Caterina Nardella, John M. Asara, Massimo Loda, Sabina Signoretti, Kaitlyn A. Webster, Christopher Ng, Andrea Lunardi, Ming Chen, Robin M. Hobbs, Antonella Papa, Mirjam T. Epping, Xue-Song Liu, Akash Patnaik, Min Sup Song, Su Jung Song, Nina Seitzer, and Enrique González-Billalabeitia

Abstract

PDF - 116K, Supplementary Materials and Methods and Supplementary Figure Legends.

Published
2023

40. Supplementary Figure 7 from Vulnerabilities of PTEN–TP53-Deficient Prostate Cancers to Compound PARP–PI3K Inhibition

Author

Pier Paolo Pandolfi, Lewis C. Cantley, John G. Clohessy, Caterina Nardella, John M. Asara, Massimo Loda, Sabina Signoretti, Kaitlyn A. Webster, Christopher Ng, Andrea Lunardi, Ming Chen, Robin M. Hobbs, Antonella Papa, Mirjam T. Epping, Xue-Song Liu, Akash Patnaik, Min Sup Song, Su Jung Song, Nina Seitzer, and Enrique González-Billalabeitia

Abstract

PDF - 138K, Survival curves of the in vivo treatment of Olaparib and BKM120.

Published
2023

41. A correlative biomarker study and integrative prognostic model in chemotherapy‐naïve metastatic castration‐resistant prostate cancer treated with enzalutamide

Author

Fernandez‐Perez, María P., primary, Perez‐Navarro, Enrique, additional, Alonso‐Gordoa, Teresa, additional, Conteduca, Vicenza, additional, Font, Albert, additional, Vázquez‐Estévez, Sergio, additional, González‐del‐Alba, Aránzazu, additional, Wetterskog, Daniel, additional, Antonarakis, Emmanuel S., additional, Mellado, Begona, additional, Fernandez‐Calvo, Ovidio, additional, Méndez‐Vidal, María J., additional, Climent, Miguel A., additional, Duran, Ignacio, additional, Gallardo, Enrique, additional, Rodriguez Sanchez, Angel, additional, Santander, Carmen, additional, Sáez, Maria I., additional, Puente, Javier, additional, Tudela, Julian, additional, Martínez, Alberto, additional, López‐Andreo, Maria J., additional, Padilla, José, additional, Lozano, Rebeca, additional, Hervas, David, additional, Luo, Jun, additional, de Giorgi, Ugo, additional, Castellano, Daniel, additional, Attard, Gerhardt, additional, Grande, Enrique, additional, and Gonzalez‐Billalabeitia, Enrique, additional

Published
2022
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42. Angiogenic role of miR-20a in breast cancer.

Author

Gines Luengo-Gil, Enrique Gonzalez-Billalabeitia, Sergio Alejo Perez-Henarejos, Esther Navarro Manzano, Asuncion Chaves-Benito, Elena Garcia-Martinez, Elisa Garcia-Garre, Vicente Vicente, and Francisco Ayala de la Peña

Subjects
Medicine, Science
Abstract

BACKGROUND:Angiogenesis is a key process for tumor progression and a target for treatment. However, the regulation of breast cancer angiogenesis and its relevance for clinical resistance to antiangiogenic drugs is still incompletely understood. Recent developments on the contribution of microRNA to tumor angiogenesis and on the oncogenic effects of miR-17-92, a miRNA cluster, point to their potential role on breast cancer angiogenesis. The aim of this work was to establish the contribution of miR-20a, a member of miR-17-92 cluster, to tumor angiogenesis in patients with invasive breast carcinoma. METHODS:Tube-formation in vitro assays with conditioned medium from MCF7 and MDA-MB-231 breast cancer cell lines were performed after transfection with miR-20a and anti-miR20a. For clinical validation of the experimental findings, we performed a retrospective analysis of a series of consecutive breast cancer patients (n = 108) treated with neoadjuvant chemotherapy and with a full characterization of their vessel pattern and expression of angiogenic markers in pre-treatment biopsies. Expression of members of the cluster miR-17-92 and of angiogenic markers was determined by RT-qPCR after RNA purification from FFPE samples. RESULTS:In vitro angiogenesis assays with endothelial cells and conditioned media from breast cancer cell lines showed that transfection with anti-miR20a in MDA-MB-231 significantly decreased mean mesh size and total mesh area, while transfection with miR-20a in MCF7 cells increased mean mesh size. MiR-20a angiogenic effects were abrogated by treatment with aflibercept, a VEGF trap. These results were supported by clinical data showing that mir-20a expression was higher in tumors with no estrogen receptor or with more extensive nodal involvement (cN2-3). A higher miR-20a expression was associated with higher mean vessel size (p = 0.015) and with an angiogenic pattern consisting in larger vessels, higher VEGFA expression and presence of glomeruloid microvascular proliferations (p

Published
2018
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43. Role of

Author

Raquel, Sopeña Sutil, Adolfo, Gómez Grande, Alejandro, González Díaz, Julio, Téigel Tobar, María Ángeles, Cabeza Rodríguez, Enrique, González Billalabeitia, and Alfredo, Rodríguez Antolín

Subjects
Male, Positron Emission Tomography Computed Tomography, Positron-Emission Tomography, Humans, Prostatic Neoplasms, Lymph Nodes, Prostate-Specific Antigen, Aged, Choline, Neoplasm Staging
Abstract

To assess the diagnostic accuracy ofTo assess the concordance betweenRetrospective observational study of 78 patients with high-risk PC undergoingThe median age was 67 years old and mean PSA was 42.39 ng/mL. The sensitivity, specificity and NPV in global initial staging for PET/CT

Published
2022

44. Transcriptional Profile Associated with Clinical Outcomes in Metastatic Hormone-Sensitive Prostate Cancer Treated with Androgen Deprivation and Docetaxel

Author

Natalia Jiménez, Òscar Reig, Mercedes Marín-Aguilera, Caterina Aversa, Laura Ferrer-Mileo, Albert Font, Alejo Rodriguez-Vida, Miguel Ángel Climent, Sara Cros, Isabel Chirivella, Montserrat Domenech, Mariona Figols, Enrique González-Billalabeitia, Daniel Jiménez Peralta, Leonardo Rodríguez-Carunchio, Samuel García-Esteve, Marta Garcia de Herreros, Maria J. Ribal, Aleix Prat, Begoña Mellado, [Jiménez N, Marín-Aguilera M] Translational Genomics and Targeted Therapeutics in Solid Tumors Lab, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain. Fundació Clínic per a la Recerca Biomèdica, Barcelona, Spain. [Reig Ò] Translational Genomics and Targeted Therapeutics in Solid Tumors Lab, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain. Fundació Clínic per a la Recerca Biomèdica, Barcelona, Spain. Medical Oncology Department, Hospital Clínic, Barcelona, Spain. Uro-Oncology Unit, Hospital Clínic, University of Barcelona, Barcelona, Spain. Department of Medicine, University of Barcelona, Barcelona, Spain. [Aversa C, Ferrer-Mileo L] ] Translational Genomics and Targeted Therapeutics in Solid Tumors Lab, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain. Fundació Clínic per a la Recerca Biomèdica, Barcelona, Spain. Medical Oncology Department, Hospital Clínic, Barcelona, Spain. Uro-Oncology Unit, Hospital Clínic, University of Barcelona, Barcelona, Spain. [Font A] Medical Oncology Department, Institut Català d’Oncologia, Hospital Germans Trias i Pujol, Badalona, Spain. [Cros S] Medical Oncology Department, Hospital General de Granollers, Granollers, Spain, and Hospital General de Granollers

Subjects
Cancer Research, Neoplasms::Neoplasms by Site::Urogenital Neoplasms::Genital Neoplasms, Male::Prostatic Neoplasms [DISEASES], Tumor suppressor genes, Pròstata - Teràpia hormonal, aminoácidos, péptidos y proteínas::proteínas::receptores citoplásmicos y nucleares::receptores de esteroides::receptores de estrógenos [COMPUESTOS QUÍMICOS Y DROGAS], metastatic prostate cancer, chemotherapy, predictive biomarkers, hormonal therapy, androgen receptor, estrogen receptor, tumor suppressor genes, Metastatic prostate cancer, Predictive biomarkers, Quimioteràpia, Chemotherapy, Estrogen receptor, Amino Acids, Peptides, and Proteins::Proteins::Receptors, Cytoplasmic and Nuclear::Receptors, Steroid::Receptors, Androgen [CHEMICALS AND DRUGS], Prostate cancer, Pròstata - Càncer, Càncer de pròstata, Amino Acids, Peptides, and Proteins::Proteins::Receptors, Cytoplasmic and Nuclear::Receptors, Steroid::Receptors, Estrogen [CHEMICALS AND DRUGS], neoplasias::neoplasias por localización::neoplasias urogenitales::neoplasias de los genitales masculinos::neoplasias de la próstata [ENFERMEDADES], Androgen receptor, Oncology, aminoácidos, péptidos y proteínas::proteínas::receptores citoplásmicos y nucleares::receptores de esteroides::receptores de andrógenos [COMPUESTOS QUÍMICOS Y DROGAS], Androgens, Hormonal therapy, Andrògens
Abstract

Simple Summary The combination of androgen deprivation therapy (ADT) with docetaxel (DX) or/and with novel anti-androgen receptor therapies have become standards for the treatment of patients with metastatic hormone-sensitive prostate cancer (mHSPC). However, metastatic PC remains incurable, and biomarkers for individual treatment selection are needed. We propose here that molecular alterations associated with castration resistance may predict the clinical evolution of mHSPC patients. To test this hypothesis, we designed a custom expression panel of 184 genes and tested it in tumor biopsies from patients with mHSPC treated with ADT+DX. We found that AR and ESR signatures and ESR2 gene expression correlate with a good prognosis. The lower expression of TSG (PTEN, TP53 and RB1) signature, as well as high ARV7 and low RB1 gene expression, were associated with adverse clinical outcomes. The usefulness of transcriptomic analysis of such signatures as a strategy for personalized treatment selection should be further explored. (1) Background: Androgen deprivation therapy (ADT) and docetaxel (DX) combination is a standard therapy for metastatic hormone-sensitive prostate cancer (mHSPC) patients. (2) Methods: We investigate if tumor transcriptomic analysis predicts mHSPC evolution in a multicenter retrospective biomarker study. A customized panel of 184 genes was tested in mRNA from tumor samples by the nCounter platform in 125 mHSPC patients treated with ADT+DX. Gene expression was correlated with castration-resistant prostate cancer-free survival (CRPC-FS) and overall survival (OS). (3) Results: High expression of androgen receptor (AR) signature was independently associated with longer CRPC-FS (hazard ratio (HR) 0.6, 95% confidence interval (CI) 0.3-0.9; p = 0.015), high expression of estrogen receptor (ESR) signature with longer CRPC-FS (HR 0.6, 95% CI 0.4-0.9; p = 0.019) and OS (HR 0.5, 95% CI 0.2-0.9, p = 0.024), and lower expression of tumor suppressor genes (TSG) (RB1, PTEN and TP53) with shorter OS (HR 2, 95% CI 1-3.8; p = 0.044). ARV7 expression was independently associated with shorter CRPC-FS (HR 1.5, 95% CI 1.1-2.1, p = 0.008) and OS (HR 1.8, 95% CI 1.2-2.6, p = 0.004), high ESR2 was associated with longer OS (HR 0.5, 95% CI 0.2-1, p = 0.048) and low expression of RB1 was independently associated with shorter OS (HR 1.9, 95% CI 1.1-3.2, p = 0.014). (4) Conclusions: AR, ESR, and TSG expression signatures, as well as ARV7, RB1, and ESR2 expression, have a prognostic value in mHSPC patients treated with ADT+DX.

Published
2022

45. Transcriptional Profile Associated with Clinical Outcomes in Metastatic Hormone-Sensitive Prostate Cancer Treated with Androgen Deprivation and Docetaxel

Author

Jiménez, Natalia, primary, Reig, Òscar, additional, Marín-Aguilera, Mercedes, additional, Aversa, Caterina, additional, Ferrer-Mileo, Laura, additional, Font, Albert, additional, Rodriguez-Vida, Alejo, additional, Climent, Miguel Ángel, additional, Cros, Sara, additional, Chirivella, Isabel, additional, Domenech, Montserrat, additional, Figols, Mariona, additional, González-Billalabeitia, Enrique, additional, Jiménez Peralta, Daniel, additional, Rodríguez-Carunchio, Leonardo, additional, García-Esteve, Samuel, additional, Garcia de Herreros, Marta, additional, Ribal, Maria J., additional, Prat, Aleix, additional, and Mellado, Begoña, additional

Published
2022
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46. Plasma androgen receptor and response to adapted and standard docetaxel regimen in castration-resistant prostate cancer: A multicenter biomarker study

Author

Rebeca Lozano, Gerhardt Attard, Ugo De Giorgi, Enrique Gonzalez-Billalabeitia, Giuseppe Schepisi, Isabel M. Aragón, Vincenza Conteduca, David Olmos, Daniel Wetterskog, Begoña Mellado, Nuria Romero-Laorden, Nicole Brighi, Emanuela Scarpi, Anuradha Jayaram, Cristian Lolli, Chiara Casadei, Mercedes Marín-Aguilera, Elena Castro, Giorgia Gurioli, Anna Wingate, Conteduca V., Wetterskog D., Castro E., Scarpi E., Romero-Laorden N., Gurioli G., Jayaram A., Lolli C., Schepisi G., Wingate A., Casadei C., Lozano R., Brighi N., Aragon I.M., Marin-Aguilera M., Gonzalez-Billalabeitia E., Mellado B., Olmos D., Attard G., and De Giorgi U.

Subjects
Adult, Male, 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Docetaxel, Drug Administration Schedule, 03 medical and health sciences, Prostate cancer, 0302 clinical medicine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Biomarkers, Tumor, medicine, Humans, Prospective Studies, Castration-resistant prostate cancer, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocol, Dose-Response Relationship, Drug, business.industry, Hazard ratio, Biomarker, Odds ratio, Middle Aged, medicine.disease, Progression-Free Survival, Confidence interval, Androgen receptor, Plasma DNA, Prospective Studie, Prostatic Neoplasms, Castration-Resistant, Regimen, 030104 developmental biology, Drug Resistance, Neoplasm, Receptors, Androgen, Dose modulation, 030220 oncology & carcinogenesis, Cohort, Prednisone, Biomarker (medicine), Drug Monitoring, business, Human, medicine.drug
Abstract

Background: Plasma AR status has been identified as a potential biomarker of response in metastatic castration-resistant prostate cancer (mCRPC) patients receiving docetaxel or AR-targeted therapies. However, the relevance of plasma AR in the overall management of CRPC patients receiving different docetaxel doses is unknown. Patients and methods: This was a multi-institution study of associations between baseline plasma AR copy number status, assessed by droplet digital PCR, and outcome in 325 mCRPC patients receiving docetaxel at standard or adapted regimen at the discretion of the treating physician. Upon analysis, patients were assigned randomly to either a training (n = 217) or validation (n = 108) cohort. Results: In the training cohort, AR-gained patients treated with adapted docetaxel regimen had a significantly worse median progression-free survival (PFS) (3.8 vs 6.3 months, hazard ratio [HR] 2.58, 95% confidence interval [CI] 1.34–4.95, p < 0.0001), median overall survival (10.8 vs 20.6 months, HR 1.98, 95% CI 1.09–3.62, p = 0.0064) and PSA response (PSA > −50%: odds ratio 4.88 95%CI 1.55–14.32, p = 0.013) as compared to plasma AR normal patients. These findings were all confirmed in the validation cohort. However, in patients treated with standard docetaxel regimen, these differences were not seen. The interaction between AR CN status and dose reduction of docetaxel was considered as independent factor for PFS in both the training and validation cohort (HR 2.84, 95% CI 1.41–5.73, p = 0.003, and HR 4.79, 95% CI 1.79–12.82, p = 0.002). Conclusion: Despite the retrospective non-randomised design of this study, our hypothesis-generating findings could suggest plasma AR as a potential biomarker for optimal docetaxel timing and dose in mCRPC patients. Prospective trials are warranted.

Published
2021

47. Resistance to the Androgen Receptor Centred Therapies: Biology and Management

Author

D. Lorente, Enrique Gonzalez-Billalabeitia, Javier Puente, Pablo Maroto, Alvaro Pinto, and A. Gómez de Liaño

Subjects
Oncology, medicine.medical_specialty, Chemotherapy, medicine.medical_treatment, General Medicine, Disease, Biology, medicine.disease, Olaparib, Targeted therapy, Androgen receptor, Prostate cancer, chemistry.chemical_compound, Docetaxel, chemistry, Internal medicine, medicine, Enzalutamide, medicine.drug
Abstract

Prostate cancer is a changeling disease. Although majority of patients show clinical and biochemical responses for long periods of time to therapies targeting the androgen receptor (AR), a small percentage of patients show intrinsic resistance. Moreover, despite dramatic responses, almost all patients will finally move from the hormone-sensitive state to the deadly castrate-resistant state, although in the castrate-resistant state, most tumours progress to AR targeted therapies through mechanisms involving the AR, but not all, and other pathways may become activated, being responsible for bypassing the AR inhibition. Once patients develop resistance to one AR targeted therapy, cross-resistance avoids in most of patients any further response to a different AR targeted therapy. The CARD trial has clearly proved that chemotherapy is superior to a sequence of AR targeted therapies in patients progressing after docetaxel and either enzalutamide or abiraterone in patients progressing before 1 year. Finally, olaparib has become the first targeted therapy not directed to the AR to prolong survival in selected patients with castrate-resistant prostate cancer. The aim of this study is to review the mechanisms of resistance to AR targeted therapies, the development of the castrate-resistant state and biomarkers to identify the castrate-resistant state and present and potential therapies to overcome the resistance to AR targeted therapies.

Published
2021

48. Estrogen receptor β and TMPRSS2-ERG expression association with clinical outcomes in metastatic hormone-sensitive prostate cancer.

Author

Aversa, Caterina, primary, Jiménez, Natalia, additional, Marin, Mercedes, additional, Ferrer-Mileo, Laura, additional, Reig, Oscar, additional, Rodriguez-Carunchio, Leonardo, additional, Font, Albert, additional, Rodriguez-Vida, Alejo, additional, Domenech-Santasusana, Montserrat, additional, Figols, Mariona, additional, Climent Duran, Miguel Angel, additional, Cros Costa, Sara, additional, Chirivella, Isabel, additional, Herrero Rivera, Daniel, additional, Gonzalez -Billalabeitia, Enrique, additional, Jiménez-Peralta, Daniel, additional, Carles, Joan, additional, Suárez, Cristina, additional, Prat, Aleix, additional, and Mellado, Begona, additional

Published
2022
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49. SEOM clinical guidelines for the treatment of advanced prostate cancer (2020)

Author

González-del-Alba, Aránzazu, Méndez-Vidal, M. J., Vazquez, S., Castro, E., Climent, Miguel Ángel, Gallardo, Eduard, Gonzalez-Billalabeitia, Enrique, Lorente, D., Maroto Rey, Pablo., Arranz Alija, Jose Ángel, and Universitat Autònoma de Barcelona

Subjects
Male, Oncology, Cancer Research, Genes, BRCA2, Genes, BRCA1, Docetaxel, Medical Oncology, Piperazines, Androgen, Prostate cancer, chemistry.chemical_compound, 0302 clinical medicine, 030212 general & internal medicine, Societies, Medical, Randomized Controlled Trials as Topic, Apalutamide, General Medicine, Combined Modality Therapy, Prostatic Neoplasms, Castration-Resistant, Darolutamide, Thiohydantoins, Cabazitaxel, 030220 oncology & carcinogenesis, Benzamides, Hormonal therapy, Androstenes, medicine.drug, medicine.medical_specialty, Clinical Guides in Oncology, Antineoplastic Agents, Olaparib, 03 medical and health sciences, Internal medicine, Nitriles, Phenylthiohydantoin, medicine, Humans, Enzalutamide, Castration, Genetic Testing, Radiotherapy, business.industry, Research, Molecular, Prostatic Neoplasms, Androgen Antagonists, medicine.disease, chemistry, Spain, Phthalazines, business, Orchiectomy, Biomarkers
Abstract

The treatment of advanced prostate cancer has evolved due to recent advances in molecular research and new drug development. Dynamic aberrations in the androgen receptor, DNA repair genes, PTEN-PI3K, and other pathways drive the behavior of advanced prostate cancer allowing a better selection of therapies in each patient. Tumor testing for BRCA1 and BRCA2 is recommended for patients with metastatic prostate cancer, also considering a broad panel to guide decisions and genetic counseling. In symptomatic metastatic patients, castration should be stared to palliate symptoms and prolong survival. In high-risk or high-volume metastatic hormone-naïve patients, castration should be combined with docetaxel, abiraterone, enzalutamide or apalutamide. Radiotherapy to the primary tumor combined with systemic therapy is recommended in low-volume mHNPC patients. In patients with non-metastatic castration-resistant tumors, risk stratification can define the frequency of imaging. Adding enzalutamide, darolutamide or apalutamide to these patients prolongs metastasis-free and overall survival, but potential adverse events need to be taken into consideration. The choice of docetaxel, abiraterone or enzalutamide for treating metastatic castration-resistant patients depends on previous therapies, with cabazitaxel being also recommended after docetaxel. Olaparib is recommended in BRCA1/BRCA2 mutated castration-resistant patients after progression on at least one new hormonal therapy. Aggressive variants of prostate cancer respond to platinum-based chemotherapy. To optimize treatment efficiency, oncologists should incorporate all of these advances into an overall therapeutic strategy.

Published
2021

50. Expert recommendations on the management of patients with metastatic castration-resistant prostate cancer who progress after CHAARTED or LATITUDE

Author

María José Méndez-Vidal, Enrique Gonzalez-Billalabeitia, Nuria Lainez, Urbano Anido, Álvaro Montesa, Miguel Angel Climent, J. P. Maroto, Javier Puente, Ángel Francisco Zazo Rodríguez, Curro Zambrana, Julio Lambea, A. González-del-Alba, [Gonzalez-del-Alba, Aranzazu] Hosp Univ Puerta Hierro Majadahonda, Med Ongol Dept, Calle Joaquin Rodrigo 2, Madrid 28222, Spain, [Puente, Javier] Hosp Clin San Carlos, CIBERONC, Inst Invest Sanitaria Hosp Clin San Carlos IdISSC, Med Oncol Dept, Madrid, Spain, [Anido, Urbano] Complejo Hosp Univ Santiago, Oncol Dept, Santiago De Compostela, Spain, [Angel Climent, Miguel] IVO, Med Oncol Dept, Valencia, Spain, [Gonzalez-Billalabeitia, Enrique] Univ Murcia, IMIB, Hosp Univ Morales Meseguer, Hematol & Med Oncol Dept, Murcia, Spain, [Gonzalez-Billalabeitia, Enrique] Univ Catolica San Antonio Murcia UCAM, Murcia, Spain, [Lainez, Nuria] Complejo Hosp Navarra, Med Oncol Dept, Pamplona, Spain, [Lambea, Julio] Hosp Clin Univ Lozano Blesa, Med Oncol Dept, Zaragoza, Spain, [Pablo Maroto, Jose] Hosp Santa Creu & Sant Pau, Med Oncol Dept, Barcelona, Spain, [Jose Mendez-Vidal, Maria] Hosp Univ Reina Sofia, Med Oncol Dept, Cordoba, Spain, [Montesa, Alvaro] Hosp Reg Malaga, Med Oncol Dept, Malaga, Spain, [Rodriguez, Angel] Hosp Leon, Med Oncol Dept, Leon, Spain, [Zambrana, Curro] Hosp Univ Infanta Sofia, Med Oncol Dept, San Sebastian De Reyes, Spain, and Sanofi

Subjects
Oncology, Radium-223, medicine.medical_specialty, radium-223, medicine.medical_treatment, Docetaxel, Androgen deprivation therapy, Castration resistant, chemotherapy, lcsh:RC254-282, 1st-line, Upfront, Increased survival, 03 medical and health sciences, chemistry.chemical_compound, Prostate cancer, 0302 clinical medicine, Internal medicine, medicine, Enzalutamide, 030212 general & internal medicine, Chemotherapy, Cabazitaxel, enzalutamide, business.industry, Abiraterone acetate, Men, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, metastatic castration-resistant prostate cancer, chemistry, 030220 oncology & carcinogenesis, androgen-deprivation therapy, business, medicine.drug
Abstract

Objective: Our aim was to provide practical recommendations on the management of patients with metastatic castration-resistant prostate cancer (mCRPC) who have progressed after docetaxel plus androgen-deprivation therapy (ADT) or abiraterone plus ADT. Methods: Systematic literature review (SLR), nominal group meeting, and Delphi process. A panel of 12 experts was established who defined the scope, users, and sections of the document. We performed an SLR in order to assess the efficacy and safety of available drugs in patients with mCRPC. Abstracts from the American Society of Oncology and European Society for Medical Oncology meetings were also examined. The results were discussed during an expert meeting in which 14 recommendations were generated. The level of agreement with the recommendations was also tested by 13 additional experts following the Delphi process. Recommendations were voted by means of scores ranging from 0 (total disagreement) to 10 (total agreement). We defined agreement when at least 70% of the experts voted ⩾7. Next, we assigned a level of evidence and grade to the recommendation using the Oxford Centre for Evidence-based Medicine Levels of Evidence, following which the final document was drafted. Results: The literature search did not find any articles meeting the inclusion criteria. Finally, 13 out of 14 recommendations were accepted after two Delphi rounds (two were modified after the first round). They pertain to general and individual case-based treatment recommendations. Conclusions: In mCRPC patients who have progressed after docetaxel or abiraterone plus ADT in the metastatic hormone-sensitive prostate cancer setting, these recommendations may support treatment decision-making, due to the lack of evidence or other globally accepted sequencing algorithms.

Published
2020

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