المؤلفون: Aliagas, Elisabet, Alay, Ania, Martínez-Iniesta, Maria, Hernández-Madrigal, Miguel, Cordero, David, Gausachs, Mireia, Pros, Eva, Saigí, Maria, Busacca, Sara, Sharkley, Annabel J, Dawson, Alan, Palmero, Ramón, Ruffinelli, José C, Padrones, Susana, Aso, Samantha, Escobar, Ignacio, Ramos, Ricard, Llatjós, Roger, Vidal, August, Dorca, Eduard, Varela, Mar, Sánchez-Céspedes, Montse, Fennell, Dean, Muñoz-Pinedo, Cristina, Villanueva, Alberto, Solé, Xavi, Nadal, Ernest

مصطلحات موضوعية: mesothelioma, preclinical models, CDK4/6 inhibitors

الوصف: Background: There is no effective therapy for patients with malignant pleural mesothelioma (MPM) who progressed to platinum-based chemotherapy and immunotherapy. Methods: We aimed to investigate the antitumor activity of CDK4/6 inhibitors using in vitro and in vivo preclinical models of MPM. Results: Based on publicly available transcriptomic data of MPM, patients with CDK4 or CDK6 overexpression had shorter overall survival. Treatment with abemaciclib or palbociclib at 100 nM significantly decreased cell proliferation in all cell models evaluated. Both CDK4/6 inhibitors significantly induced G1 cell cycle arrest, thereby increasing cell senescence and increased the expression of interferon signalling pathway and tumour antigen presentation process in culture models of MPM. In vivo preclinical studies showed that palbociclib significantly reduced tumour growth and prolonged overall survival using distinct xenograft models of MPM implanted in athymic mice. Conclusions: Treatment of MPM with CDK4/6 inhibitors decreased cell proliferation, mainly by promoting cell cycle arrest at G1 and by induction of cell senescence. Our preclinical studies provide evidence for evaluating CDK4/6 inhibitors in the clinic for the treatment of MPM.

العلاقة: info:eu-repo/grantAgreement/EC/H2020/766214/; https://zenodo.org/record/5599000Test; https://doi.org/10.1038/s41416-021-01547-yTest; oai:zenodo.org:5599000

الإتاحة: https://doi.org/10.1038/s41416-021-01547-yTest
https://zenodo.org/record/5599000Test

المؤلفون: Grande, Enrique, Teulé, Alex, Alonso-Gordoa, Teresa, Jiménez-Fonseca, Paula, Benavent, Marta, Capdevila, Jaume, Custodio, Ana, Vera, Ruth, Munarriz, Javier, La Casta, Adelaida, Díez, Juan José, Gajate, Pablo, Molina-Cerrillo, Javier, Matos, Ignacio, Cristóbal, Eva María, Ruffinelli, José C, Palacios, José, García-Carbonero, Rocío

مصطلحات موضوعية: Antineoplastic Combined Chemotherapy Protocols, Female, Humans, Male, Middle Aged, Neuroendocrine Tumors, Pancreatic Neoplasms, Piperazines, Pyridines, Spain

الوصف: Palbociclib demonstrated no detectable activity in molecularly unselected and heavily pretreated patients with advanced grade 1/2 pancreatic neuroendocrine tumors. Predictive biomarkers that improve patient selection should be investigated in future studies of palbociclib. Palbociclib, a CDK4/6 inhibitor, has shown in vitro activity in pancreatic neuroendocrine tumor (pNET) cell lines. Here we prospectively assessed the activity and safety of palbociclib in monotherapy in metastatic refractory pNETs. This was a nonrandomized, open-label, phase II study of patients with metastatic grade (G)1/2 pNETs recruited from 10 centers in Spain. Palbociclib 125 mg was orally administered once daily for 21 of 28 days until disease progression or unacceptable toxicity. Twenty-one patients were included; 52.4% were men, and median age was 57.4 years (range, 37.4-73.4). Patients had previously received a median of three prior lines of systemic therapy (range, 1-10) for advanced disease (somatostatin analogues, 71.4%; sunitinib, 81.0%; everolimus, 47.6%; chemotherapy, 47.6%). Nineteen patients were evaluated for objective response rate (ORR), with a median follow-up of 12.4 months (range, 7.53-19.33). No objective and confirmed responses were observed (0%); 11 (57.9%) patients had stable disease, and 6 of them lasted more than 6 months; 8 (42.1%) patients had disease progression as best response. Median progression-free survival (PFS) was 2.6 months (95% confidence interval [CI], 0-14.4) and median overall survival (OS) was 18.7 months (95% CI, 7.4-29.9; Fig. 1). Most frequent toxicities of any grade were asthenia (76.2%), neutropenia (42.9%), diarrhea (33.3%), and nausea (33.3%). Five (23.8%) patients developed G3-4 neutropenia and two (9.5%) patients developed G3-4 thrombocytopenia. Lack of activity was observed with palbociclib as a single agent in molecularly unselected and heavily pretreated patients with advanced G1/2 pNETs.

العلاقة: http://hdl.handle.net/10668/15086Test; PMC7485337; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7485337/pdfTest

الإتاحة: https://doi.org/10.1634/theoncologist.2020-0033Test
http://hdl.handle.net/10668/15086Test
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7485337/pdfTest

المؤلفون: Duruisseaux, Michäel, Martínez-Cardús, Anna, Calleja-Cervantes, Maria E, Moran, Sebastian, Castro de Moura, Manuel, Davalos, Veronica, Piñeyro, David, Sanchez-Cespedes, Montse, Girard, Nicolas, Brevet, Marie, Giroux-Leprieur, Etienne, Dumenil, Coraline, Pradotto, Monica, Bironzo, Paolo, Capelletto, Enrica, Novello, Silvia, Cortot, Alexis, Copin, Marie-Christine, Karachaliou, Niki, Gonzalez-Cao, Maria, Peralta, Sergio, Montuenga, Luis M, Gil-Bazo, Ignacio, Baraibar, Iosune, Lozano, Maria D, Varela, Mar, Ruffinelli, Jose C, Palmero, Ramon, Nadal, Ernest, MORAN GONZALEZ, MARIA TERESA, Perez, Lidia, Ramos, Immaculada, Xiao, Qingyang, Fernandez, Agustin F, Fraga, Mario F, Gut, Marta, Gut, Ivo, Teixidó, Cristina, Vilariño, Noelia, Prat, Aleix, Reguart, Noemi, Benito, Amparo, Garrido, Pilar, Barragan, Isabel, Emile, Jean-François, Rosell, Rafael, Brambilla, Elisabeth, Esteller, Manel

المساهمون: Duruisseaux, Michäel, Martínez-Cardús, Anna, Calleja-Cervantes, Maria E, Moran, Sebastian, Castro de Moura, Manuel, Davalos, Veronica, Piñeyro, David, Sanchez-Cespedes, Montse, Girard, Nicola, Brevet, Marie, Giroux-Leprieur, Etienne, Dumenil, Coraline, Pradotto, Monica, Bironzo, Paolo, Capelletto, Enrica, Novello, Silvia, Cortot, Alexi, Copin, Marie-Christine, Karachaliou, Niki, Gonzalez-Cao, Maria, Peralta, Sergio, Montuenga, Luis M, Gil-Bazo, Ignacio, Baraibar, Iosune, Lozano, Maria D, Varela, Mar, Ruffinelli, Jose C, Palmero, Ramon, Nadal, Ernest, Moran, Teresa, Perez, Lidia, Ramos, Immaculada, Xiao, Qingyang, Fernandez, Agustin F, Fraga, Mario F, Gut, Marta, Gut, Ivo, Teixidó, Cristina, Vilariño, Noelia, Prat, Aleix, Reguart, Noemi, Benito, Amparo, Garrido, Pilar, Barragan, Isabel, Emile, Jean-Françoi, Rosell, Rafael, Brambilla, Elisabeth, Esteller, Manel

مصطلحات موضوعية: Pulmonary and Respiratory Medicine

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/30100403; info:eu-repo/semantics/altIdentifier/wos/WOS:000445806700021; volume:6; issue:10; firstpage:771; lastpage:781; numberofpages:11; journal:THE LANCET RESPIRATORY MEDICINE; http://hdl.handle.net/2318/1685285Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85053827989; http://www.elsevier.com/journals/the-lancet-respiratory-medicine/2213-2600Test; http://diposit.ub.edu/dspace/bitstream/2445/125743/1/Esteller_Test 2018.pdf

الإتاحة: https://doi.org/10.1016/S2213-2600Test(18)30284-4
http://hdl.handle.net/2318/1685285Test
http://www.elsevier.com/journals/the-lancet-respiratory-medicine/2213-2600Test
http://diposit.ub.edu/dspace/bitstream/2445/125743/1/Esteller_Test 2018.pdf

المؤلفون: Van Cutsem, Eric, Taieb, Julien, Yaeger, Rona, Yoshino, Takayuki, Grothey, Axel, Maiello, Evaristo, Elez, Elena, Dekervel, Jeroen, Ross, Paul, Ruiz-Casado, Ana, Graham, Janet, Kato, Takeshi, Ruffinelli, Jose C., André, Thierry, Carrière Roussel, Edith, Klauck, Isabelle, Groc, Mélanie, Vedovato, Jean-Claude, Tabernero, Josep

الوصف: Purpose: The positive BEACON colorectal cancer (CRC) safety lead-in, evaluating encorafenib + cetuximab + binimetinib in previously treated patients with BRAFV600E-mutated metastatic CRC (mCRC), prompted the design of the phase II ANCHOR CRC study (ClinicalTrails.gov identifier: NCT03693170). ANCHOR CRC aimed to evaluate efficacy, safety, and quality of life with first-line encorafenib + binimetinib + cetuximab in BRAFV600E-mutated mCRC. Methods: In this multicenter, open-label, single-arm study, patients with BRAFV600E-mutated mCRC received oral encorafenib 300 mg once daily and binimetinib 45 mg twice daily in 28-day cycles, plus intravenous cetuximab 400 mg/m2 once on Day 1 of Cycle 1, then 250 mg/m2 once weekly for the first seven cycles, and 500 mg/m2 once on Days 1 and 15 from Cycle 8 onward. The primary end point was locally assessed confirmed objective response rate (cORR), and secondary end points included centrally assessed cORR, progression-free survival, overall survival (OS), quality of life, and safety and tolerability. Results: Among 95 patients, the locally assessed cORR was 47.4% (95% CI, 37.0 to 57.9) with all partial responses. Since the lower limit of the 95% CI exceeded 30%, the primary end point was met. With a median follow-up duration of 20.1 months, the median progression-free survival on the basis of local assessments was 5.8 months and the median OS was 18.3 months. Treatment was well tolerated, with no unexpected toxicities. Using Patient Global Impression of Changes, substantial improvement in symptoms was consistently reported in ≥ 30% of patients from Cycle 3 to Cycle 10. Conclusion: The ANCHOR CRC study showed that the scientifically driven combination of encorafenib + binimetinib + cetuximab was active in the first-line setting of BRAFV600E-mutated mCRC with a manageable safety profile. Further first-line evaluation is ongoing (ClinicalTrails.gov identifier: NCT04607421).

وصف الملف: text

العلاقة: https://eprints.gla.ac.uk/292416/1/292416.pdfTest; Van Cutsem, E. et al. (2023) ANCHOR CRC: results from a single-arm, phase II study of encorafenib plus binimetinib and cetuximab in previously untreated BRAFV600E-mutant metastatic colorectal cancer. Journal of Clinical Oncology , 41(14), pp. 2628-2637. (doi:10.1200/JCO.22.01693 ) (PMID:36763936)

الإتاحة: https://doi.org/10.1200/JCO.22.01693Test
https://eprints.gla.ac.uk/292416Test/
https://eprints.gla.ac.uk/292416/1/292416.pdfTest

المؤلفون: Aparicio, Inmaculada, Iranzo, Patricia, Reyes, Roxana, Bote, Helena, Saigi, María, Bringas, Marianela, Bosch-Barrera, Joaquim, Corral, Jesús, Aparisi, Francisco, Ruffinelli, Jose C., Jiménez, Beatriz, Lage, Yolanda, López-Castro, Rafael, Majem, Margarita, Vázquez, Sergio, Artal, Ángel, Rodríguez-Pérez, Ángel, Lázaro-Quintela, Martín, Torres, José Miguel Sánchez, Reguart, Noemí, Cucurull, Marc, Gil-Bazo, Ignacio, Camps, Carlos, Nadal, Ernest, del Barrio, Anabel, Garrido, Pilar, Dómine, Manuel, Álvarez, Rosa, Muñoz, Andrés J., Calles, Antonio

المصدر: Thrombosis Research ; volume 232, page 133-137 ; ISSN 0049-3848

مصطلحات موضوعية: Hematology

الإتاحة: https://doi.org/10.1016/j.thromres.2023.11.007Test
https://api.elsevier.com/content/article/PII:S0049384823003134?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S0049384823003134?httpAccept=text/plainTest

المؤلفون: Antonio, Maite, Saldaña, Juana, Linares, Jennifer, Ruffinelli, José C, Palmero, Ramón, Navarro, Arturo, Arnaiz, Maria Dolores, Brao, Isabel, Aso, Samantha, Padrones, Susana, Navarro, Valentí, González-Barboteo, Jesús, Borràs, Josep Maria, Cardenal, Felipe, Nadal, Ernest

المصدر: British Journal of Cancer ; volume 118, issue 5, page 639-647 ; ISSN 0007-0920 1532-1827

مصطلحات موضوعية: Cancer Research, Oncology

الإتاحة: https://doi.org/10.1038/bjc.2017.455Test
http://www.nature.com/articles/bjc2017455.pdfTest
http://www.nature.com/articles/bjc2017455Test

المؤلفون: Mezquita, Laura, Preeshagul, Isabel, Auclin, Edouard, Saravia, Diana, Hendriks, Lizza, Rizvi, Hira, Park, Wungki, Nadal, Ernest, Martin-Romano, Patricia, Ruffinelli, Jose C, Ponce, Santiago, Audigier-Valette, Clarisse, Carnio, Simona, Blanc-Durand, Felix, Bironzo, Paolo, Tabbò, Fabrizio, Reale, Maria Lucia, Novello, Silvia, Hellmann, Matthew D, Sawan, Peter, Girshman, Jeffrey, Plodkowski, Andrew J, Zalcman, Gerard, Majem, Margarita, Charrier, Melinda, Naigeon, Marie, Rossoni, Caroline, Mariniello, AnnaPaola, Paz-Ares, Luis, Dingemans, Anne Marie, Planchard, David, Cozic, Nathalie, Cassard, Lydie, Lopes, Gilberto, Chaput, Nathalie, Arbour, Kathryn, Besse, Benjamin

المساهمون: Mezquita, Laura, Preeshagul, Isabel, Auclin, Edouard, Saravia, Diana, Hendriks, Lizza, Rizvi, Hira, Park, Wungki, Nadal, Ernest, Martin-Romano, Patricia, Ruffinelli, Jose C, Ponce, Santiago, Audigier-Valette, Clarisse, Carnio, Simona, Blanc-Durand, Felix, Bironzo, Paolo, Tabbò, Fabrizio, Reale, Maria Lucia, Novello, Silvia, Hellmann, Matthew D, Sawan, Peter, Girshman, Jeffrey, Plodkowski, Andrew J, Zalcman, Gerard, Majem, Margarita, Charrier, Melinda, Naigeon, Marie, Rossoni, Caroline, Mariniello, AnnaPaola, Paz-Ares, Lui, Dingemans, Anne Marie, Planchard, David, Cozic, Nathalie, Cassard, Lydie, Lopes, Gilberto, Chaput, Nathalie, Arbour, Kathryn, Besse, Benjamin

مصطلحات موضوعية: Biomarker, Immunotherapy, NSCLC, Neutrophil, dNLR

الوصف: dNLR at the baseline (B), defined by neutrophils/[leucocytes-neutrophils], correlates with immune-checkpoint inhibitor (ICI) outcomes in advanced non-small-cell lung cancer (aNSCLC). However, dNLR is dynamic under therapy and its longitudinal assessment may provide data predicting efficacy. We sought to examine the impact of dNLR dynamics on ICI efficacy and understand its biological significance.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/34022698; info:eu-repo/semantics/altIdentifier/wos/WOS:000660301100021; volume:151; firstpage:211; lastpage:220; numberofpages:10; journal:EUROPEAN JOURNAL OF CANCER; http://hdl.handle.net/2318/1790644Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85106271256

الإتاحة: https://doi.org/10.1016/j.ejca.2021.03.011Test
http://hdl.handle.net/2318/1790644Test