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1. Copy number alterations in metastatic and early breast tumours: prognostic and acquired biomarkers of resistance to CDK4/6 inhibitors

Author

Sablin, Marie-Paule, Gestraud, Pierre, Jonas, Sarah Flora, Lamy, Constance, Lacroix-Triki, Magali, Bachelot, Thomas, Filleron, Thomas, Lacroix, Ludovic, Tran-Dien, Alicia, Jézéquel, Pascal, Mauduit, Marjorie, Barros Monteiro, Janice, Jimenez, Marta, Michiels, Stefan, Attignon, Valery, Soubeyran, Isabelle, Driouch, Keltouma, Servant, Nicolas, Le Tourneau, Christophe, Kamal, Maud, André, Fabrice, and Bièche, Ivan

Published
2024
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3. Integrated High-Throughput Screening and Large-Scale Isobolographic Analysis to Accelerate the Discovery of Radiosensitizers With Greater Selectivity for Cancer Cells

Author

Verrelle, Pierre, Gestraud, Pierre, Poyer, Florent, Soria, Adèle, Tessier, Sarah, Lescure, Aurianne, Anthony, Elodie, Corbé, Maxime, Heinrich, Sophie, Beauvineau, Claire, Chaput, Ludovic, Granzhan, Anton, Piguel, Sandrine, Perez, Franck, Teulade-Fichou, Marie-Paule, Megnin-Chanet, Frédérique, and Del Nery, Elaine

Published
2024
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4. A druggable copper-signalling pathway that drives inflammation

Author

Solier, Stéphanie, Müller, Sebastian, Cañeque, Tatiana, Versini, Antoine, Mansart, Arnaud, Sindikubwabo, Fabien, Baron, Leeroy, Emam, Laila, Gestraud, Pierre, Pantoș, G. Dan, Gandon, Vincent, Gaillet, Christine, Wu, Ting-Di, Dingli, Florent, Loew, Damarys, Baulande, Sylvain, Durand, Sylvère, Sencio, Valentin, Robil, Cyril, Trottein, François, Péricat, David, Näser, Emmanuelle, Cougoule, Céline, Meunier, Etienne, Bègue, Anne-Laure, Salmon, Hélène, Manel, Nicolas, Puisieux, Alain, Watson, Sarah, Dawson, Mark A., Servant, Nicolas, Kroemer, Guido, Annane, Djillali, and Rodriguez, Raphaël

Published
2023
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5. Genomics to select treatment for patients with metastatic breast cancer

Author

Andre, Fabrice, Filleron, Thomas, Kamal, Maud, Mosele, Fernanda, Arnedos, Monica, Dalenc, Florence, Sablin, Marie-Paule, Campone, Mario, Bonnefoi, Hervé, Lefeuvre-Plesse, Claudia, Jacot, William, Coussy, Florence, Ferrero, Jean-Marc, Emile, George, Mouret-Reynier, Marie-Ange, Thery, Jean-Christophe, Isambert, Nicolas, Mege, Alice, Barthelemy, Philippe, You, Benoit, Hajjaji, Nawale, Lacroix, Ludovic, Rouleau, Etienne, Tran-Dien, Alicia, Boyault, Sandrine, Attignon, Valery, Gestraud, Pierre, Servant, Nicolas, Le Tourneau, Christophe, Cherif, Linda Larbi, Soubeyran, Isabelle, Montemurro, Filippo, Morel, Alain, Lusque, Amelie, Jimenez, Marta, Jacquet, Alexandra, Gonçalves, Anthony, Bachelot, Thomas, and Bieche, Ivan

Published
2022
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6. Abstract A009: Synthetic lethality in the context of STAG2-mutant Ewing sarcoma

Author

Mous, Lieke, primary, Hofer, Michelle, additional, Zabėlė, Dorita, additional, Bechtold, Ingrid, additional, Zaidi, Sakina, additional, Fouassier, Camille, additional, Gestraud, Pierre, additional, Boré, Aurélien, additional, Margueron, Raphaël, additional, Wachtel, Marco, additional, Schäfer, Beat, additional, Delattre, Olivier, additional, and Surdez, Didier, additional

Published
2024
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7. Molecular profiling of non-small-cell lung cancer patients with or without brain metastases included in the randomized SAFIR02-LUNG trial and association with intracranial outcome

Author

Mogenet, Alice, Barlesi, Fabrice, Besse, Benjamin, Michiels, Stefan, Karimi, Maryam, Tran-Dien, Alicia, Girard, Nicolas, Mazieres, Julien, Audigier-Valette, Clarisse, Locatelli-Sanchez, Myriam, Kamal, Maud, Gestraud, Pierre, Hamza, Abderaouf, Jacquet, Alexandra, Jimenez, Marta, Yara, Sabrina, Greillier, Laurent, Bertucci, François, Planchard, David, Soria, Jean-Charles, Bieche, Ivan, and Tomasini, Pascale

Published
2022
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8. RAS activation induces synthetic lethality of MEK inhibition with mitochondrial oxidative metabolism in acute myeloid leukemia

Author

Decroocq, Justine, Birsen, Rudy, Montersino, Camille, Chaskar, Prasad, Mano, Jordi, Poulain, Laury, Friedrich, Chloe, Alary, Anne-Sophie, Guermouche, Helene, Sahal, Ambrine, Fouquet, Guillemette, Gotanègre, Mathilde, Simonetta, Federico, Mouche, Sarah, Gestraud, Pierre, Lescure, Auriane, Del Nery, Elaine, Bosc, Claudie, Grenier, Adrien, Mazed, Fetta, Mondesir, Johanna, Chapuis, Nicolas, Ho, Liza, Boughalem, Aicha, Lelorc’h, Marc, Gobeaux, Camille, Fontenay, Michaela, Recher, Christian, Vey, Norbert, Guillé, Arnaud, Birnbaum, Daniel, Hermine, Olivier, Radford-Weiss, Isabelle, Tsantoulis, Petros, Collette, Yves, Castellano, Rémy, Sarry, Jean-Emmanuel, Pasmant, Eric, Bouscary, Didier, Kosmider, Olivier, and Tamburini, Jerome

Published
2022
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9. Metastatic renal cell carcinoma with occult primary: a multicenter prospective cohort.

Author

Jacquin, Nicolas, Flippot, Ronan, Masliah-Planchon, Julien, Grisay, Guillaume, Brillet, Riwan, Dupain, Célia, Kamal, Maud, Guillou, Isabelle, Gruel, Nadège, Servant, Nicolas, Gestraud, Pierre, Wong, Jennifer, Cockenpot, Vincent, Goncalves, Andreia, Selves, Janick, Blons, Hélène, Rouleau, Etienne, Delattre, Olivier, Gervais, Claire, and Le Tourneau, Christophe

Subjects
TREATMENT effectiveness, CANCER of unknown primary origin, DIAGNOSIS, OCCULTISM, METASTASIS
Abstract

Metastatic carcinoma of presumed renal origin (rCUP) has recently emerged as a new entity within the heterogeneous entity of Cancers of Unknown Primary (CUP) but their biological features and optimal therapeutic management remain unknown. We report the molecular characteristics and clinical outcome of a series of 25 rCUP prospectively identified within the French National Multidisciplinary Tumor Board for CUP. This cohort strongly suggests that rCUP share similarities with common RCC subtypes and benefit from renal-tailored systemic treatment. This study highlights the importance of integrating clinical and molecular data for optimal diagnosis and management of CUP. [ABSTRACT FROM AUTHOR]

Published
2024
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10. Intronic polyadenylation isoforms in the 5’ part of genes constitute a source of microproteins and are involved in cell response to cisplatin

Author

Devaux, Alexandre, primary, Tanaka, Iris, additional, Cadix, Mandy, additional, Heneman-Masurel, Amélie, additional, Michallet, Sophie, additional, Fouilleul, Quentin, additional, Chakraborty, Alina, additional, Labbe, Céline M., additional, Fontrodona, Nicolas, additional, Claude, Jean-Baptiste, additional, Deloger, Marc, additional, Gestraud, Pierre, additional, Tessier, Ludovic, additional, Mortada, Hussein, additional, Lameiras, Sonia, additional, Raynal, Virginie, additional, Baulande, Sylvain, additional, Servant, Nicolas, additional, Auboeuf, Didier, additional, Eymin, Béatrice, additional, Vagner, Stéphan, additional, and Dutertre, Martin, additional

Published
2023
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11. The influence of feature selection methods on accuracy, stability and interpretability of molecular signatures

Author

Haury, Anne-Claire, Gestraud, Pierre, and Vert, Jean-Philippe

Subjects
Quantitative Biology - Quantitative Methods, Statistics - Applications, Statistics - Machine Learning
Abstract

Motivation: Biomarker discovery from high-dimensional data is a crucial problem with enormous applications in biology and medicine. It is also extremely challenging from a statistical viewpoint, but surprisingly few studies have investigated the relative strengths and weaknesses of the plethora of existing feature selection methods. Methods: We compare 32 feature selection methods on 4 public gene expression datasets for breast cancer prognosis, in terms of predictive performance, stability and functional interpretability of the signatures they produce. Results: We observe that the feature selection method has a significant influence on the accuracy, stability and interpretability of signatures. Simple filter methods generally outperform more complex embedded or wrapper methods, and ensemble feature selection has generally no positive effect. Overall a simple Student's t-test seems to provide the best results. Availability: Code and data are publicly available at http://cbio.ensmp.fr/~ahaury/.

Published
2011
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12. Integrated high-throughput screening and large-scale isobolographic analysis to accelerate the discovery of radiosensitizers with greater selectivity for cancer cells

Author

Verrelle, Pierre, primary, Gestraud, Pierre, additional, Poyer, Florent, additional, Soria, Adèle, additional, Tessier, Sarah, additional, Lescure, Aurianne, additional, Anthony, Elodie, additional, Corbé, Maxime, additional, Henrich, Sophie, additional, Beauvineau, Claire, additional, Chaput, Ludovic, additional, Granzhan, Anton, additional, Piguel, Sandrine, additional, Perez, Franck, additional, Teulade-Fichou, Marie-Paule, additional, Megnin-Chanet, Frédérique, additional, and Nery, Elaine Del, additional

Published
2023
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13. MET functions in tumour progression and therapy resistance are repressed by intronic polyadenylation

Author

Boldina, Galina, primary, Vallejos, Maricarmen, additional, Allard, Delphine, additional, Cadix, Mandy, additional, Labbe, Celine, additional, Vacher, Sophie, additional, Hemmingsson, Oskar, additional, Gestraud, Pierre, additional, Teissandier, Aurelie, additional, Martineau, Sylvain, additional, Auboeuf, Didier, additional, Andre, Fabrice, additional, Kamal, Maud, additional, Servant, Nicolas, additional, Bieche, Ivan, additional, Dutertre, Martin, additional, Robert, Caroline, additional, and Vagner, Stephan, additional

Published
2023
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14. Data from Combination Therapies Targeting ALK-aberrant Neuroblastoma in Preclinical Models

Author

Tucker, Elizabeth R., primary, Jiménez, Irene, primary, Chen, Lindi, primary, Bellini, Angela, primary, Gorrini, Chiara, primary, Calton, Elizabeth, primary, Gao, Qiong, primary, Che, Harvey, primary, Poon, Evon, primary, Jamin, Yann, primary, Martins Da Costa, Barbara, primary, Barker, Karen, primary, Shrestha, Sumana, primary, Hutchinson, J. Ciaran, primary, Dhariwal, Simran, primary, Goodman, Angharad, primary, Del Nery, Elaine, primary, Gestraud, Pierre, primary, Bhalshankar, Jaydutt, primary, Iddir, Yasmine, primary, Saberi-Ansari, Elnaz, primary, Saint-Charles, Alexandra, primary, Geoerger, Birgit, primary, Marques Da Costa, Maria Eugénia, primary, Pierre-Eugène, Cécile, primary, Janoueix-Lerosey, Isabelle, primary, Decaudin, Didier, primary, Nemati, Fariba, primary, Carcaboso, Angel M., primary, Surdez, Didier, primary, Delattre, Olivier, primary, George, Sally L., primary, Chesler, Louis, primary, Tweddle, Deborah A., primary, and Schleiermacher, Gudrun, primary

Published
2023
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15. Figure S2 from Combination Therapies Targeting ALK-aberrant Neuroblastoma in Preclinical Models

Author

Tucker, Elizabeth R., primary, Jiménez, Irene, primary, Chen, Lindi, primary, Bellini, Angela, primary, Gorrini, Chiara, primary, Calton, Elizabeth, primary, Gao, Qiong, primary, Che, Harvey, primary, Poon, Evon, primary, Jamin, Yann, primary, Martins Da Costa, Barbara, primary, Barker, Karen, primary, Shrestha, Sumana, primary, Hutchinson, J. Ciaran, primary, Dhariwal, Simran, primary, Goodman, Angharad, primary, Del Nery, Elaine, primary, Gestraud, Pierre, primary, Bhalshankar, Jaydutt, primary, Iddir, Yasmine, primary, Saberi-Ansari, Elnaz, primary, Saint-Charles, Alexandra, primary, Geoerger, Birgit, primary, Marques Da Costa, Maria Eugénia, primary, Pierre-Eugène, Cécile, primary, Janoueix-Lerosey, Isabelle, primary, Decaudin, Didier, primary, Nemati, Fariba, primary, Carcaboso, Angel M., primary, Surdez, Didier, primary, Delattre, Olivier, primary, George, Sally L., primary, Chesler, Louis, primary, Tweddle, Deborah A., primary, and Schleiermacher, Gudrun, primary

Published
2023
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16. Supplementary Data DS1 from Combination Therapies Targeting ALK-aberrant Neuroblastoma in Preclinical Models

Author

Tucker, Elizabeth R., primary, Jiménez, Irene, primary, Chen, Lindi, primary, Bellini, Angela, primary, Gorrini, Chiara, primary, Calton, Elizabeth, primary, Gao, Qiong, primary, Che, Harvey, primary, Poon, Evon, primary, Jamin, Yann, primary, Martins Da Costa, Barbara, primary, Barker, Karen, primary, Shrestha, Sumana, primary, Hutchinson, J. Ciaran, primary, Dhariwal, Simran, primary, Goodman, Angharad, primary, Del Nery, Elaine, primary, Gestraud, Pierre, primary, Bhalshankar, Jaydutt, primary, Iddir, Yasmine, primary, Saberi-Ansari, Elnaz, primary, Saint-Charles, Alexandra, primary, Geoerger, Birgit, primary, Marques Da Costa, Maria Eugénia, primary, Pierre-Eugène, Cécile, primary, Janoueix-Lerosey, Isabelle, primary, Decaudin, Didier, primary, Nemati, Fariba, primary, Carcaboso, Angel M., primary, Surdez, Didier, primary, Delattre, Olivier, primary, George, Sally L., primary, Chesler, Louis, primary, Tweddle, Deborah A., primary, and Schleiermacher, Gudrun, primary

Published
2023
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17. Supplementary material 2. from Enhancing Abiraterone Acetate Efficacy in Androgen Receptor–positive Triple-negative Breast Cancer: Chk1 as a Potential Target

Author

Grellety, Thomas, primary, Callens, Celine, primary, Richard, Elodie, primary, Briaux, Adrien, primary, Vélasco, Valérie, primary, Pulido, Marina, primary, Gonçalves, Anthony, primary, Gestraud, Pierre, primary, MacGrogan, Gaetan, primary, Bonnefoi, Hervé, primary, and Cardinaud, Bruno, primary

Published
2023
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18. Supplementary Data Legend from Enhancing Abiraterone Acetate Efficacy in Androgen Receptor–positive Triple-negative Breast Cancer: Chk1 as a Potential Target

Author

Grellety, Thomas, primary, Callens, Celine, primary, Richard, Elodie, primary, Briaux, Adrien, primary, Vélasco, Valérie, primary, Pulido, Marina, primary, Gonçalves, Anthony, primary, Gestraud, Pierre, primary, MacGrogan, Gaetan, primary, Bonnefoi, Hervé, primary, and Cardinaud, Bruno, primary

Published
2023
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19. Supplementary material 1. from Enhancing Abiraterone Acetate Efficacy in Androgen Receptor–positive Triple-negative Breast Cancer: Chk1 as a Potential Target

Author

Grellety, Thomas, primary, Callens, Celine, primary, Richard, Elodie, primary, Briaux, Adrien, primary, Vélasco, Valérie, primary, Pulido, Marina, primary, Gonçalves, Anthony, primary, Gestraud, Pierre, primary, MacGrogan, Gaetan, primary, Bonnefoi, Hervé, primary, and Cardinaud, Bruno, primary

Published
2023
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20. Supplementary figure S2. from Enhancing Abiraterone Acetate Efficacy in Androgen Receptor–positive Triple-negative Breast Cancer: Chk1 as a Potential Target

Author

Grellety, Thomas, primary, Callens, Celine, primary, Richard, Elodie, primary, Briaux, Adrien, primary, Vélasco, Valérie, primary, Pulido, Marina, primary, Gonçalves, Anthony, primary, Gestraud, Pierre, primary, MacGrogan, Gaetan, primary, Bonnefoi, Hervé, primary, and Cardinaud, Bruno, primary

Published
2023
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22. Supplementary material 3. from Enhancing Abiraterone Acetate Efficacy in Androgen Receptor–positive Triple-negative Breast Cancer: Chk1 as a Potential Target

Author

Grellety, Thomas, primary, Callens, Celine, primary, Richard, Elodie, primary, Briaux, Adrien, primary, Vélasco, Valérie, primary, Pulido, Marina, primary, Gonçalves, Anthony, primary, Gestraud, Pierre, primary, MacGrogan, Gaetan, primary, Bonnefoi, Hervé, primary, and Cardinaud, Bruno, primary

Published
2023
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23. Combination Therapies Targeting ALK-aberrant Neuroblastoma in Preclinical Models

Author

Tucker, Elizabeth R; https://orcid.org/0000-0003-3716-6605, Jiménez, Irene; https://orcid.org/0000-0002-3544-4045, Chen, Lindi; https://orcid.org/0000-0001-7223-4226, Bellini, Angela; https://orcid.org/0000-0001-7374-1887, Gorrini, Chiara; https://orcid.org/0000-0002-5239-6671, Calton, Elizabeth; https://orcid.org/0000-0002-3662-8401, Gao, Qiong; https://orcid.org/0000-0002-0406-1594, Che, Harvey; https://orcid.org/0000-0003-1011-4653, Poon, Evon; https://orcid.org/0000-0002-0616-2487, Jamin, Yann; https://orcid.org/0000-0003-0350-3757, Da Costa, Barbara Martins; https://orcid.org/0000-0002-8993-6790, Barker, Karen; https://orcid.org/0000-0002-2357-3894, Shrestha, Sumana; https://orcid.org/0000-0002-5368-0818, Hutchinson, J Ciaran; https://orcid.org/0000-0002-1708-2634, Dhariwal, Simran; https://orcid.org/0000-0003-2386-9748, Goodman, Angharad; https://orcid.org/0000-0002-3010-5757, Del Nery, Elaine; https://orcid.org/0000-0002-9654-5202, Gestraud, Pierre; https://orcid.org/0000-0002-3893-9879, Bhalshankar, Jaydutt; https://orcid.org/0000-0001-7184-943X, Iddir, Yasmine; https://orcid.org/0000-0002-7022-0725, Saberi-Ansari, Elnaz; https://orcid.org/0000-0003-2472-1075, Saint-Charles, Alexandra; https://orcid.org/0000-0001-7779-7669, Geoerger, Birgit; https://orcid.org/0000-0003-4361-3643, Da Costa, Maria Eugénia Marques; https://orcid.org/0000-0002-1498-603X, Pierre-Eugène, Cécile; https://orcid.org/0000-0002-0351-7211, Janoueix-Lerosey, Isabelle; https://orcid.org/0000-0003-0434-3003, Decaudin, Didier; https://orcid.org/0000-0003-2254-0043, Nemati, Fariba; https://orcid.org/0000-0001-8879-7592, Carcaboso, Angel M; https://orcid.org/0000-0002-8485-426X, Surdez, Didier; https://orcid.org/0000-0002-7118-7859, et al, Tucker, Elizabeth R; https://orcid.org/0000-0003-3716-6605, Jiménez, Irene; https://orcid.org/0000-0002-3544-4045, Chen, Lindi; https://orcid.org/0000-0001-7223-4226, Bellini, Angela; https://orcid.org/0000-0001-7374-1887, Gorrini, Chiara; https://orcid.org/0000-0002-5239-6671, Calton, Elizabeth; https://orcid.org/0000-0002-3662-8401, Gao, Qiong; https://orcid.org/0000-0002-0406-1594, Che, Harvey; https://orcid.org/0000-0003-1011-4653, Poon, Evon; https://orcid.org/0000-0002-0616-2487, Jamin, Yann; https://orcid.org/0000-0003-0350-3757, Da Costa, Barbara Martins; https://orcid.org/0000-0002-8993-6790, Barker, Karen; https://orcid.org/0000-0002-2357-3894, Shrestha, Sumana; https://orcid.org/0000-0002-5368-0818, Hutchinson, J Ciaran; https://orcid.org/0000-0002-1708-2634, Dhariwal, Simran; https://orcid.org/0000-0003-2386-9748, Goodman, Angharad; https://orcid.org/0000-0002-3010-5757, Del Nery, Elaine; https://orcid.org/0000-0002-9654-5202, Gestraud, Pierre; https://orcid.org/0000-0002-3893-9879, Bhalshankar, Jaydutt; https://orcid.org/0000-0001-7184-943X, Iddir, Yasmine; https://orcid.org/0000-0002-7022-0725, Saberi-Ansari, Elnaz; https://orcid.org/0000-0003-2472-1075, Saint-Charles, Alexandra; https://orcid.org/0000-0001-7779-7669, Geoerger, Birgit; https://orcid.org/0000-0003-4361-3643, Da Costa, Maria Eugénia Marques; https://orcid.org/0000-0002-1498-603X, Pierre-Eugène, Cécile; https://orcid.org/0000-0002-0351-7211, Janoueix-Lerosey, Isabelle; https://orcid.org/0000-0003-0434-3003, Decaudin, Didier; https://orcid.org/0000-0003-2254-0043, Nemati, Fariba; https://orcid.org/0000-0001-8879-7592, Carcaboso, Angel M; https://orcid.org/0000-0002-8485-426X, Surdez, Didier; https://orcid.org/0000-0002-7118-7859, and et al

Abstract

PURPOSE ALK-activating mutations are identified in approximately 10% of newly diagnosed neuroblastomas and ALK amplifications in a further 1%-2% of cases. Lorlatinib, a third-generation anaplastic lymphoma kinase (ALK) inhibitor, will soon be given alongside induction chemotherapy for children with ALK-aberrant neuroblastoma. However, resistance to single-agent treatment has been reported and therapies that improve the response duration are urgently required. We studied the preclinical combination of lorlatinib with chemotherapy, or with the MDM2 inhibitor, idasanutlin, as recent data have suggested that ALK inhibitor resistance can be overcome through activation of the p53-MDM2 pathway. EXPERIMENTAL DESIGN We compared different ALK inhibitors in preclinical models prior to evaluating lorlatinib in combination with chemotherapy or idasanutlin. We developed a triple chemotherapy (CAV: cyclophosphamide, doxorubicin, and vincristine) in vivo dosing schedule and applied this to both neuroblastoma genetically engineered mouse models (GEMM) and patient-derived xenografts (PDX). RESULTS Lorlatinib in combination with chemotherapy was synergistic in immunocompetent neuroblastoma GEMM. Significant growth inhibition in response to lorlatinib was only observed in the ALK-amplified PDX model with high ALK expression. In this PDX, lorlatinib combined with idasanutlin resulted in complete tumor regression and significantly delayed tumor regrowth. CONCLUSIONS In our preclinical neuroblastoma models, high ALK expression was associated with lorlatinib response alone or in combination with either chemotherapy or idasanutlin. The synergy between MDM2 and ALK inhibition warrants further evaluation of this combination as a potential clinical approach for children with neuroblastoma.

Published
2023

24. Combination Therapies Targeting ALK-aberrant Neuroblastoma in Preclinical Models

Author

Tucker, Elizabeth R., primary, Jiménez, Irene, additional, Chen, Lindi, additional, Bellini, Angela, additional, Gorrini, Chiara, additional, Calton, Elizabeth, additional, Gao, Qiong, additional, Che, Harvey, additional, Poon, Evon, additional, Jamin, Yann, additional, Martins Da Costa, Barbara, additional, Barker, Karen, additional, Shrestha, Sumana, additional, Hutchinson, J. Ciaran, additional, Dhariwal, Simran, additional, Goodman, Angharad, additional, Del Nery, Elaine, additional, Gestraud, Pierre, additional, Bhalshankar, Jaydutt, additional, Iddir, Yasmine, additional, Saberi-Ansari, Elnaz, additional, Saint-Charles, Alexandra, additional, Geoerger, Birgit, additional, Marques Da Costa, Maria Eugénia, additional, Pierre-Eugène, Cécile, additional, Janoueix-Lerosey, Isabelle, additional, Decaudin, Didier, additional, Nemati, Fariba, additional, Carcaboso, Angel M., additional, Surdez, Didier, additional, Delattre, Olivier, additional, George, Sally L., additional, Chesler, Louis, additional, Tweddle, Deborah A., additional, and Schleiermacher, Gudrun, additional

Published
2023
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26. COMBINATION THERAPIES TARGETING ALK-ABERRANT NEUROBLASTOMA IN PRECLINICAL MODELS

Author

Tucker, Elizabeth R., primary, Jiménez, Irene, additional, Chen, Lindi, additional, Bellini, Angela, additional, Gorrini, Chiara, additional, Calton, Elizabeth, additional, Gao, Qiong, additional, Che, Harvey, additional, Poon, Evon, additional, Jamin, Yann, additional, Martins da Costa, Barbara, additional, Barker, Karen, additional, Shrestha, Sumana, additional, Hutchinson, J. Ciaran, additional, Dhariwal, Simran, additional, Goodman, Angharad, additional, Del Nery, Elaine, additional, Gestraud, Pierre, additional, Bhalshankar, Jaydutt, additional, Iddir, Yasmine, additional, Saberi-Ansari, Elnaz, additional, Saint-Charles, Alexandra, additional, Geoerger, Birgit, additional, Marques Da Costa, Maria Eugénia, additional, Pierre-Eugène, Cécile, additional, Janoueix-Lerosey, Isabelle, additional, Decaudin, Didier, additional, Nemati, Fariba, additional, Carcaboso, Angel M., additional, Surdez, Didier, additional, Delattre, Olivier, additional, George, Sally L., additional, Chesler, Louis, additional, Tweddle, Deborah A., additional, and Schleiermacher, Gudrun, additional

Published
2022
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27. Relevance of the TRIAP1/p53 axis in colon cancer cell proliferation and adaptation to glutamine deprivation

Author

Nedara, Kenza, primary, Reinhardt, Camille, additional, Lebraud, Emilie, additional, Arena, Giuseppe, additional, Gracia, Céline, additional, Buard, Valérie, additional, Pioche-Durieu, Catherine, additional, Castelli, Florence, additional, Colsch, Benoit, additional, Bénit, Paule, additional, Rustin, Pierre, additional, Albaud, Benoit, additional, Gestraud, Pierre, additional, Baulande, Sylvain, additional, Servant, Nicolas, additional, Deutsch, Eric, additional, Verbavatz, Jean-Marc, additional, Brenner, Catherine, additional, Milliat, Fabien, additional, and Modjtahedi, Nazanine, additional

Published
2022
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28. DNA methylation restricts coordinated germline and neural fates in embryonic stem cell differentiation

Author

Schulz, Mathieu, primary, Teissandier, Aurélie, additional, de la Mata, Elena, additional, Armand, Mélanie, additional, Iranzo, Julian, additional, El Marjou, Fatima, additional, Gestraud, Pierre, additional, Walter, Marius, additional, Kinston, Sarah, additional, Göttgens, Berthold, additional, Greenberg, Maxim V.C., additional, and Bourc’his, Deborah, additional

Published
2022
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29. A catalog of numerical centrosome defects in epithelial ovarian cancers

Author

Morretton, Jean‐Philippe, primary, Simon, Anthony, additional, Herbette, Aurélie, additional, Barbazan, Jorge, additional, Pérez‐González, Carlos, additional, Cosson, Camille, additional, Mboup, Bassirou, additional, Latouche, Aurélien, additional, Popova, Tatiana, additional, Kieffer, Yann, additional, Macé, Anne‐Sophie, additional, Gestraud, Pierre, additional, Bataillon, Guillaume, additional, Becette, Véronique, additional, Meseure, Didier, additional, Nicolas, André, additional, Mariani, Odette, additional, Vincent‐Salomon, Anne, additional, Stern, Marc‐Henri, additional, Mechta‐Grigoriou, Fatima, additional, Roman Roman, Sergio, additional, Vignjevic, Danijela Matic, additional, Rouzier, Roman, additional, Sastre‐Garau, Xavier, additional, Goundiam, Oumou, additional, and Basto, Renata, additional

Published
2022
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31. Compartment-specific and ELAVL1-coordinated regulation of intronic polyadenylation isoforms by doxorubicin

Author

Chakraborty, Alina, primary, Cadix, Mandy, additional, Relier, Sébastien, additional, Taricco, Nicolò, additional, Alaeitabar, Tina, additional, Devaux, Alexandre, additional, Labbé, Céline M., additional, Martineau, Sylvain, additional, Heneman-Masurel, Amélie, additional, Gestraud, Pierre, additional, Inga, Alberto, additional, Servant, Nicolas, additional, Vagner, Stéphan, additional, and Dutertre, Martin, additional

Published
2022
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32. Relevance of the TRIAP1/p53 axis in colon cancer cell proliferation and adaptation to glutamine deprivation

Author

Nedara, Kenza, Reinhardt, Camille, Lebraud, Emilie, Arena, Giuseppe, Gracia, Céline, Buard, Valérie, Pioche-Durieu, Catherine, Castelli, Florence, Colsch, Benoit, Bénit, Paule, Rustin, Pierre, Albaud, Benoit, Gestraud, Pierre, Baulande, Sylvain, Servant, Nicolas, Deutsch, Eric, Verbavatz, Jean-Marc, Brenner, Catherine, Milliat, Fabien, Modjtahedi, Nazanine, Nedara, Kenza, Reinhardt, Camille, Lebraud, Emilie, Arena, Giuseppe, Gracia, Céline, Buard, Valérie, Pioche-Durieu, Catherine, Castelli, Florence, Colsch, Benoit, Bénit, Paule, Rustin, Pierre, Albaud, Benoit, Gestraud, Pierre, Baulande, Sylvain, Servant, Nicolas, Deutsch, Eric, Verbavatz, Jean-Marc, Brenner, Catherine, Milliat, Fabien, and Modjtahedi, Nazanine

Abstract

Human TRIAP1 (TP53-regulated inhibitor of apoptosis 1; also known as p53CSV for p53-inducible cell survival factor) is the homolog of yeast Mdm35, a well-known chaperone that interacts with the Ups/PRELI family proteins and participates in the intramitochondrial transfer of lipids for the synthesis of cardiolipin (CL) and phosphatidylethanolamine. Although recent reports indicate that TRIAP1 is a prosurvival factor abnormally overexpressed in various types of cancer, knowledge about its molecular and metabolic function in human cells is still elusive. It is therefore critical to understand the metabolic and proliferative advantages that TRIAP1 expression provides to cancer cells. Here, in a colorectal cancer cell model, we report that the expression of TRIAP1 supports cancer cell proliferation and tumorigenesis. Depletion of TRIAP1 perturbed the mitochondrial ultrastructure, without a major impact on CL levels and mitochondrial activity. TRIAP1 depletion caused extramitochondrial perturbations resulting in changes in the endoplasmic reticulum-dependent lipid homeostasis and induction of a p53-mediated stress response. Furthermore, we observed that TRIAP1 depletion conferred a robust p53-mediated resistance to the metabolic stress caused by glutamine deprivation. These findings highlight the importance of TRIAP1 in tumorigenesis and indicate that the loss of TRIAP1 has extramitochondrial consequences that could impact on the metabolic plasticity of cancer cells and their response to conditions of nutrient deprivation.

Published
2022

33. Discovery of a druggable copper-signaling pathway that drives cell plasticity and inflammation

Author

Solier, Stephanie, primary, Muller, Sebastian, additional, Caneque, Tatiana, additional, Versini, Antoine, additional, Baron, Leeroy, additional, Gestraud, Pierre, additional, Servant, Nicolas, additional, Emam, Laila, additional, Mansart, Arnaud, additional, Pantos, G. Dan, additional, Gandon, Vincent, additional, Sencio, Valentin, additional, Robin, Cyril, additional, Trottein, Francois, additional, Begue, Anne-Laure, additional, Salmon, Helene, additional, Durand, Sylvere, additional, Wu, Ting-Di, additional, Manel, Nicolas, additional, Puisieux, Alain, additional, Dawson, Mark A., additional, Watson, Sarah, additional, Kroemer, Guido, additional, Annane, Djillali, additional, and Rodriguez, Raphael, additional

Published
2022
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34. In vivo genome-wide CRISPR screens identify SOCS1 as intrinsic checkpoint of CD4 + T H 1 cell response

Author

Sutra Del Galy, Aurélien, primary, Menegatti, Silvia, additional, Fuentealba, Jaime, additional, Lucibello, Francesca, additional, Perrin, Laetitia, additional, Helft, Julie, additional, Darbois, Aurélie, additional, Saitakis, Michael, additional, Tosello, Jimena, additional, Rookhuizen, Derek, additional, Deloger, Marc, additional, Gestraud, Pierre, additional, Socié, Gérard, additional, Amigorena, Sebastian, additional, Lantz, Olivier, additional, and Menger, Laurie, additional

Published
2021
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35. Centrosome amplification favours survival and impairs ovarian cancer progression

Author

Morretton, Jean-Philippe, Herbette, Aurélie, Cosson, Camille, Mboup, Bassirou, Latouche, Aurélien, Gestraud, Pierre, Popova, Tatiana, Stern, Marc-Henri, Nemati, Fariba, Decaudin, Didier, Bataillon, Guillaume, Becette, Véronique, Meseure, Didier, Nicolas, André, Mariani, Odette, Bonneau, Claire, Barbazan, Jorge, Vincent-Salomon, Anne, Mechta-Grigoriou, Fatima, Roman, Sergio Roman, Rouzier, Roman, Sastre-Garau, Xavier, Goundiam, Oumou, Basto, Renata, Centre de recherche de l'Institut Curie [Paris], and Institut Curie [Paris]

Subjects
[SDV]Life Sciences [q-bio]
Abstract

Centrosome amplification has been described as a common feature of human cancers and it is known to promote tumorigenesis when induced in animals. However, little is known about the real status of centrosome numbers in human cancers and whether numerical alterations are solely associated with poor prognosis. To address this question, we have analyzed a large cohort of human epithelial ovarian cancers (EOCs) from 100 patients using state-of-the-art microscopy to determine the Centrosome-Nucleus Index (CNI) of each tumor. We found that EOCs are highly heterogeneous, with infrequent but strong centrosome amplifications leading to higher CNI than in healthy tissues. Strikingly, while a correlation between CNI and genomic alterations, such as aneuploidy or chromosome rearrangements could not be established, we found that high CNI correlates with increased patient survival and sensitivity to chemotherapy. Using ovarian cancer cellular models to manipulate centrosome numbers and Patient-Derived Xenografts (PDXs), we found that higher CNIs can positively impact the response to chemotherapy and inhibit cell dissemination. Our findings highlight a novel paradigm linking centrosome amplification to the inhibition of tumor progression.

Published
2021

38. In vivo genome-wide CRISPR screens identify SOCS1 as a major intrinsic checkpoint of CD4+ Th1 cell response

Author

Del Galy, Aurélien Sutra, primary, Menegatti, Silvia, additional, Fuentealba, Jaime, additional, Perrin, Laetitia, additional, Lucibello, Francesca, additional, Helft, Julie, additional, Darbois, Aurélie, additional, Saitakis, Michael, additional, Tosello, Jimena, additional, Rookhuizen, Derek, additional, Deloger, Marc, additional, Gestraud, Pierre, additional, Socié, Gérard, additional, Amigorena, Sebastian, additional, Lantz, Olivier, additional, and Menger, Laurie, additional

Published
2021
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39. Corrigendum to ‘clinical and genetic landscape of treatment naive cervical cancer: Alterations in PIK3CA and in epigenetic modulators associated with sub-optimal outcome’ (EBioMedicine (2019) 43 (253–260), (S2352396419302142), (10.1016/j.ebiom.2019.03.069))

Author

Scholl, Suzy, Popovic, Marina, de la Rochefordiere, Anne, Girard, Elodie, Dureau, Sylvain, Mandic, Aljosa, Koprivsek, Katarina, Samet, Nina, Craina, Marius, Margan, Madalin, Samuels, Sanne, Zijlmans, Henry, Kenter, Gemma, Hillemanns, Peter, Dema, Sorin, Dema, Alis, Malenkovic, Goran, Djuran, Branislav, Floquet, Anne, Garbay, Delphine, Guyon, Federic, Colombo, Pierre Emmanuel, Fabbro, Michel, Kerr, Christine, Ngo, Charlotte, Lecuru, Fabrice, del Campo, Eleonor Rivin, Coutant, Charles, Marchal, Frederic, Mesgouez-Nebout, Nathalie, Fourchotte, Virginie, Feron, Jean Guillaume, Morice, Philippe, Deutsch, Eric, Wimberger, Pauline, Classe, Jean-Marc, Gleeson, Noreen, von der Leyen, Heiko, Minsat, Mathieu, Dubot, Coraline, Gestraud, Pierre, Kereszt, Attila, Nagy, Istvan, Balint, Balazs, Berns, Els, Jordanova, Ekaterina, de Saint-Jorre, Nicolas, Savignoni, Alexia, Servant, Nicolas, Hupe, Philippe, de Koning, Leanne, Fumoleau, Pierre, Rouzier, Roman, Kamal, Maud, Obstetrics and gynaecology, CCA - Cancer biology and immunology, and Amsterdam Reproduction & Development (AR&D)

Abstract

The authors wish to clarify that the authors Aljosa Mandic, Katarina Koprivsek, and Goran Malenkovic are also affiliated with Faculty of Medicine Novi Sad, University of Novi Sad, Serbia, as well as Gynecologic Oncology Department Clinic for Operative Oncology, Institute of Oncology of Vojvodina, Serbia.

Published
2020

40. Corrigendum to ‘clinical and genetic landscape of treatment naive cervical cancer:Alterations in PIK3CA and in epigenetic modulators associated with sub-optimal outcome’ (EBioMedicine (2019) 43 (253–260), (S2352396419302142), (10.1016/j.ebiom.2019.03.069))

Author

Scholl, Suzy, Popovic, Marina, de la Rochefordiere, Anne, Girard, Elodie, Dureau, Sylvain, Mandic, Aljosa, Koprivsek, Katarina, Samet, Nina, Craina, Marius, Margan, Madalin, Samuels, Sanne, Zijlmans, Henry, Kenter, Gemma, Hillemanns, Peter, Dema, Sorin, Dema, Alis, Malenkovic, Goran, Djuran, Branislav, Floquet, Anne, Garbay, Delphine, Guyon, Federic, Colombo, Pierre Emmanuel, Fabbro, Michel, Kerr, Christine, Ngo, Charlotte, Lecuru, Fabrice, del Campo, Eleonor Rivin, Coutant, Charles, Marchal, Frederic, Mesgouez-Nebout, Nathalie, Fourchotte, Virginie, Feron, Jean Guillaume, Morice, Philippe, Deutsch, Eric, Wimberger, Pauline, Classe, Jean-Marc, Gleeson, Noreen, von der Leyen, Heiko, Minsat, Mathieu, Dubot, Coraline, Gestraud, Pierre, Kereszt, Attila, Nagy, Istvan, Balint, Balazs, Berns, Els, Jordanova, Ekaterina, de Saint-Jorre, Nicolas, Savignoni, Alexia, Servant, Nicolas, Hupe, Philippe, de Koning, Leanne, Fumoleau, Pierre, Rouzier, Roman, and Kamal, Maud

Abstract

The authors wish to clarify that the authors Aljosa Mandic, Katarina Koprivsek, and Goran Malenkovic are also affiliated with Faculty of Medicine Novi Sad, University of Novi Sad, Serbia, as well as Gynecologic Oncology Department Clinic for Operative Oncology, Institute of Oncology of Vojvodina, Serbia.

Published
2020

41. Human chromosome-specific aneuploidy is influenced by DNA-dependent centromeric features

Author

CMM Groep Lens, Cancer, Hubrecht Institute with UMC, Dumont, Marie, Gamba, Riccardo, Gestraud, Pierre, Klaasen, Sjoerd, Worrall, Joseph T., De Vries, Sippe G., Boudreau, Vincent, Salinas-Luypaert, Catalina, Maddox, Paul S., Lens, Susanne M.A., Kops, Geert J.P.L., McClelland, Sarah E., Miga, Karen H., Fachinetti, Daniele, CMM Groep Lens, Cancer, Hubrecht Institute with UMC, Dumont, Marie, Gamba, Riccardo, Gestraud, Pierre, Klaasen, Sjoerd, Worrall, Joseph T., De Vries, Sippe G., Boudreau, Vincent, Salinas-Luypaert, Catalina, Maddox, Paul S., Lens, Susanne M.A., Kops, Geert J.P.L., McClelland, Sarah E., Miga, Karen H., and Fachinetti, Daniele

Published
2020

43. Genetic markers and phosphoprotein forms of beta-catenin pβ-Cat552 and pβ-Cat675 are prognostic biomarkers of cervical cancer

Author

Scholl, Suzy M, primary, Beal, Jonas, additional, de Koning, Leanne, additional, Girard, Elodie, additional, Popovic, Marina, additional, de la Rochefordière, Anne, additional, Lecuru, Fabrice, additional, Fourchotte, Virginie, additional, Ngo, Charlotte, additional, Floquet, Anne, additional, Berns, Els MJJ, additional, Kenter, Gemma, additional, Gestraud, Pierre, additional, von der Leyen, Heiko, additional, Lecerf, Charlotte, additional, Puard, Vincent, additional, Roman, Sergio Roman, additional, Latouche, Aurelien, additional, Kereszt, Attila, additional, Balint, Balazs, additional, Rouzier, Roman, additional, and Kamal, Maud, additional

Published
2020
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44. Fine‐needle aspiration as an alternative to core needle biopsy for tumour molecular profiling in precision oncology: prospective comparative study of next‐generation sequencing in cancer patients included in the SHIVA02 trial

Author

Dupain, Célia, primary, Masliah‐Planchon, Julien, additional, Gu, Céline, additional, Girard, Elodie, additional, Gestraud, Pierre, additional, Du Rusquec, Pauline, additional, Borcoman, Edith, additional, Bello, Diana, additional, Ricci, Francesco, additional, Hescot, Ségolène, additional, Sablin, Marie‐Paule, additional, Tresca, Patricia, additional, Moura, Alexandre, additional, Loirat, Delphine, additional, Frelaut, Maxime, additional, Vincent‐Salomon, Anne, additional, Lecerf, Charlotte, additional, Callens, Céline, additional, Antonio, Samantha, additional, Franck, Coralie, additional, Mariani, Odette, additional, Bièche, Ivan, additional, Kamal, Maud, additional, Le Tourneau, Christophe, additional, and Servois, Vincent, additional

Published
2020
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45. Abstract A43: Centrosome amplification favors survival and impairs ovarian cancer progression

Author

Morretton, Jean-Philippe, primary, Herbette, Aurelie, additional, Cosson, Camille, additional, Mboup, Bassirou, additional, Latouche, Aurelien, additional, Gestraud, Pierre, additional, Popova, Tatiana, additional, Stern, Marc-Henri, additional, Nemati, Fariba, additional, Decaudin, Didier, additional, Bataillon, Guillaume, additional, Becette, Veronique, additional, Meseure, Didier, additional, Nicolas, Andre, additional, Mariani, Odette, additional, Bonneau, Claire, additional, Barbazan, Jorge, additional, Vincent-Salomon, Anne, additional, Mechta-Grigoriou, Fatima, additional, Roman-Roman, Sergio, additional, Rouzier, Roman, additional, Sastre-Garau, Xavier, additional, Goundiam, Oumou, additional, and Basto, Renata, additional

Published
2020
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46. In vivo genome-wide CRISPR screens identify SOCS1 as intrinsic checkpoint of CD4+ TH1 cell response.

Author

Sutra Del Galy, Aurélien, Menegatti, Silvia, Fuentealba, Jaime, Lucibello, Francesca, Perrin, Laetitia, Helft, Julie, Darbois, Aurélie, Saitakis, Michael, Tosello, Jimena, Rookhuizen, Derek, Deloger, Marc, Gestraud, Pierre, Socié, Gérard, Amigorena, Sebastian, Lantz, Olivier, and Menger, Laurie

Abstract

A key to the CAR: The therapeutic effects of adoptive T cell therapy (ATCT) are influenced by limited clonal expansion of antigen-experienced CD4+ T cells, which restrict their own proliferation after transfer. The cell-intrinsic factors that regulate clonal proliferation of antigen-experienced CD4+ T cells are not well defined. Sutra Del Galy et al. performed an in vivo genome-wide CRISPR screen to identify genes that controlled antigen-specific CD4+ T cell proliferation after transfer. They identified SOCS1 as a critical node that functions downstream of IFN-γ and IL-2 signaling to inhibit CD4+ T cell proliferation, survival, and effector function. Inactivation of SOCS1 in human CAR-T cells improved antitumor responses, indicating that SOCS1 is a major negative checkpoint in ATCT, representing an attractive target for optimizing CAR-T cell therapies. Although CD8+ T cells undergo autonomous clonal proliferation after antigen stimulation in vivo, the expansion of activated CD4+ T cells is limited by intrinsic factors that are poorly characterized. Using genome-wide CRISPR-Cas9 screens and an in vivo system modeling of antigen-experienced CD4+ T cell recruitment and proliferation during a localized immune response, we identified suppressor of cytokine signaling 1 (SOCS1) as a major nonredundant checkpoint imposing a brake on CD4+ T cell proliferation. Using anti–interleukin-2 receptor (IL-2R) blocking antibodies, interferon-γ receptor (IFN-γR) knockout mice, and transcriptomic analysis, we show that SOCS1 is a critical node integrating both IL-2 and IFN-γ signals to block multiple downstream signaling pathways abrogating CD4+ T helper 1 (TH1) cell response. Inactivation of SOCS1 in both murine and human CD4+ T cell antitumor adoptive therapies restored intratumor accumulation, proliferation/survival, persistence, and polyfunctionality and promoted rejection of established tumors. However, in CD8+ T cells, SOCS1 deletion did not affect the proliferation but rather improved survival and effector functions, which allowed for optimal therapeutic outcome when associated with SOCS1 inactivation in CD4+ T cells. Together, these findings identify SOCS1 as a major intracellular negative checkpoint of adoptive T cell response, opening new possibilities to optimize CAR-T cell therapy composition and efficacy. [ABSTRACT FROM AUTHOR]

Published
2021
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47. Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen

Author

Menden, Michael P., Wang, Dennis, Mason, Mike J., Szalai, Bence, Bulusu, Krishna C., Guan, Yuanfang, Yu, Thomas, Kang, Jaewoo, Jeon, Minji, Wolfinger, Russ, Nguyen, Tin, Zaslavskiy, Mikhail, Jang, In Sock, Ghazoui, Zara, Ahsen, Mehmet Eren, Vogel, Robert, Neto, Elias Chaibub, Norman, Thea, Tang, Eric K. Y., Garnett, Mathew J., Di Veroli, Giovanni Y., Fawell, Stephen, Stolovitzky, Gustavo, Guinney, Justin, Dry, Jonathan R., Saez-Rodriguez, Julio, Abante, Jordi, Abecassis, Barbara Schmitz, Aben, Nanne, Aghamirzaie, Delasa, Aittokallio, Tero, Akhtari, Farida S., Al-lazikani, Bissan, Alam, Tanvir, Allam, Amin, Allen, Chad, de Almeida, Mariana Pelicano, Altarawy, Doaa, Alves, Vinicius, Amadoz, Alicia, Anchang, Benedict, Antolin, Albert A., Ash, Jeremy R., Romeo Aznar, Victoria, Ba-alawi, Wail, Bagheri, Moeen, Bajic, Vladimir, Ball, Gordon, Ballester, Pedro J., Baptista, Delora, Bare, Christopher, Bateson, Mathilde, Bender, Andreas, Bertrand, Denis, Wijayawardena, Bhagya, Boroevich, Keith A., Bosdriesz, Evert, Bougouffa, Salim, Bounova, Gergana, Brouwer, Thomas, Bryant, Barbara, Calaza, Manuel, Calderone, Alberto, Calza, Stefano, Capuzzi, Stephen, Carbonell-Caballero, Jose, Carlin, Daniel, Carter, Hannah, Castagnoli, Luisa, Celebi, Remzi, Cesareni, Gianni, Chang, Hyeokyoon, Chen, Guocai, Chen, Haoran, Chen, Huiyuan, Cheng, Lijun, Chernomoretz, Ariel, Chicco, Davide, Cho, Kwang-Hyun, Cho, Sunghwan, Choi, Daeseon, Choi, Jaejoon, Choi, Kwanghun, Choi, Minsoo, De Cock, Martine, Coker, Elizabeth, Cortes-Ciriano, Isidro, Cserzo, Miklos, Cubuk, Cankut, Curtis, Christina, Van Daele, Dries, Dang, Cuong C., Dijkstra, Tjeerd, Dopazo, Joaquin, Draghici, Sorin, Drosou, Anastasios, Dumontier, Michel, Ehrhart, Friederike, Eid, Fatma-Elzahraa, ElHefnawi, Mahmoud, Elmarakeby, Haitham A., van Engelen, Bo, Engin, Hatice Billur, de Esch, Iwan, Evelo, Chris, Falcao, Andre O., Farag, Sherif, Fernandez-Lozano, Carlos, Fisch, Kathleen, Flobak, Asmund, Fornari, Chiara, Foroushani, Amir B. K., Fotso, Donatien Chedom, Fourches, Denis, Friend, Stephen, Frigessi, Arnoldo, Gao, Feng, Gao, Xiaoting, Gerold, Jeffrey M., Gestraud, Pierre, Ghosh, Samik, Gillberg, Jussi, Godoy-Lorite, Antonia, Godynyuk, Lizzy, Godzik, Adam, Goldenberg, Anna, Gomez-Cabrero, David, Gonen, Mehmet, de Graaf, Chris, Gray, Harry, Grechkin, Maxim, Guimera, Roger, Guney, Emre, Haibe-Kains, Benjamin, Han, Younghyun, Hase, Takeshi, He, Di, He, Liye, Heath, Lenwood S., Hellton, Kristoffer H., Helmer-Citterich, Manuela, Hidalgo, Marta R., Hidru, Daniel, Hill, Steven M., Hochreiter, Sepp, Hong, Seungpyo, Hovig, Eivind, Hsueh, Ya-Chih, Hu, Zhiyuan, Huang, Justin K., Huang, R. Stephanie, Hunyady, Laszlo, Hwang, Jinseub, Hwang, Tae Hyun, Hwang, Woochang, Hwang, Yongdeuk, Isayev, Olexandr, Walk, Oliver Bear Don't, Jack, John, Jahandideh, Samad, Ji, Jiadong, Jo, Yousang, Kamola, Piotr J., Kanev, Georgi K., Karacosta, Loukia, Karimi, Mostafa, Kaski, Samuel, Kazanov, Marat, Khamis, Abdullah M., Khan, Suleiman Ali, Kiani, Narsis A., Kim, Allen, Kim, Jinhan, Kim, Juntae, Kim, Kiseong, Kim, Kyung, Kim, Sunkyu, Kim, Yongsoo, Kim, Yunseong, Kirk, Paul D. W., Kitano, Hiroaki, Klambauer, Gunter, Knowles, David, Ko, Melissa, Kohn-Luque, Alvaro, Kooistra, Albert J., Kuenemann, Melaine A., Kuiper, Martin, Kurz, Christoph, Kwon, Mijin, van Laarhoven, Twan, Laegreid, Astrid, Lederer, Simone, Lee, Heewon, Lee, Jeon, Lee, Yun Woo, Leppaho, Eemeli, Lewis, Richard, Li, Jing, Li, Lang, Liley, James, Lim, Weng Khong, Lin, Chieh, Liu, Yiyi, Lopez, Yosvany, Low, Joshua, Lysenko, Artem, Machado, Daniel, Madhukar, Neel, De Maeyer, Dries, Malpartida, Ana Belen, Mamitsuka, Hiroshi, Marabita, Francesco, Marchal, Kathleen, Marttinen, Pekka, Mason, Daniel, Mazaheri, Alireza, Mehmood, Arfa, Mehreen, Ali, Michaut, Magali, Miller, Ryan A., Mitsopoulos, Costas, Modos, Dezso, Van Moerbeke, Marijke, Moo, Keagan, Motsinger-Reif, Alison, Movva, Rajiv, Muraru, Sebastian, Muratov, Eugene, Mushthofa, Mushthofa, Nagarajan, Niranjan, Nakken, Sigve, Nath, Aritro, Neuvial, Pierre, Newton, Richard, Ning, Zheng, De Niz, Carlos, Oliva, Baldo, Olsen, Catharina, Palmeri, Antonio, Panesar, Bhawan, Papadopoulos, Stavros, Park, Jaesub, Park, Seonyeong, Park, Sungjoon, Pawitan, Yudi, Peluso, Daniele, Pendyala, Sriram, Peng, Jian, Perfetto, Livia, Pirro, Stefano, Plevritis, Sylvia, Politi, Regina, Poon, Hoifung, Porta, Eduard, Prellner, Isak, Preuer, Kristina, Angel Pujana, Miguel, Ramnarine, Ricardo, Reid, John E., Reyal, Fabien, Richardson, Sylvia, Ricketts, Camir, Rieswijk, Linda, Rocha, Miguel, Rodriguez-Gonzalvez, Carmen, Roell, Kyle, Rotroff, Daniel, de Ruiter, Julian R., Rukawa, Ploy, Sadacca, Benjamin, Safikhani, Zhaleh, Safitri, Fita, Sales-Pardo, Marta, Sauer, Sebastian, Schlichting, Moritz, Seoane, Jose A., Serra, Jordi, Shang, Ming-Mei, Sharma, Alok, Sharma, Hari, Shen, Yang, Shiga, Motoki, Shin, Moonshik, Shkedy, Ziv, Shopsowitz, Kevin, Sinai, Sam, Skola, Dylan, Smirnov, Petr, Soerensen, Izel Fourie, Soerensen, Peter, Song, Je-Hoon, Song, Sang Ok, Soufan, Othman, Spitzmueller, Andreas, Steipe, Boris, Suphavilai, Chayaporn, Tamayo, Sergio Pulido, Tamborero, David, Tang, Jing, Tanoli, Zia-ur-Rehman, Tarres-Deulofeu, Marc, Tegner, Jesper, Thommesen, Liv, Tonekaboni, Seyed Ali Madani, Tran, Hong T., De Troyer, Ewoud, Truong, Amy, Tsunoda, Tatsuhiko, Turu, Gabor, Tzeng, Guang-Yo, Verbeke, Lieven, Videla, Santiago, Vis, Daniel, Voronkov, Andrey, Votis, Konstantinos, Wang, Ashley, Wang, Hong-Qiang Horace, Wang, Po-Wei, Wang, Sheng, Wang, Wei, Wang, Xiaochen, Wang, Xin, Wennerberg, Krister, Wernisch, Lorenz, Wessels, Lodewyk, van Westen, Gerard J. P., Westerman, Bart A., White, Simon Richard, Willighagen, Egon, Wurdinger, Tom, Xie, Lei, Xie, Shuilian, Xu, Hua, Yadav, Bhagwan, Yau, Christopher, Yeerna, Huwate, Yin, Jia Wei, Yu, Michael, Yu, MinHwan, Yun, So Jeong, Zakharov, Alexey, Zamichos, Alexandros, Zanin, Massimiliano, Zeng, Li, Zenil, Hector, Zhang, Frederick, Zhang, Pengyue, Zhang, Wei, Zhao, Hongyu, Zhao, Lan, Zheng, Wenjin, Zoufir, Azedine, Zucknick, Manuela, and Computer Science

Subjects
health care economics and organizations
Abstract

The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca's large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells. AstraZeneca European Union Horizon 2020 research [668858 PrECISE] Joint Research Center for Computational Biomedicine (Bayer AG) National Institute for Health Research (NIHR) Sheffield Biomedical Research Center, Premium Postdoctoral Fellowship Program of the Hungarian Academy of Sciences Wellcome Trust [102696, 206194] We thank the Genomics of Drug Sensitivity in Cancer and COSMIC teams at the Wellcome Trust Sanger Institute for help with the preparation of the molecular data, Denes Turei for help with Omnipath, and Katjusa Koler for help with matching drug names across combination screens. We thank AstraZeneca for funding and provision of data to the DREAM Consortium to run the challenge, and funding from the European Union Horizon 2020 research (under grant agreement No 668858 PrECISE to J.S.R.), the Joint Research Center for Computational Biomedicine (which is partially funded by Bayer AG) to J.S.R., National Institute for Health Research (NIHR) Sheffield Biomedical Research Center, Premium Postdoctoral Fellowship Program of the Hungarian Academy of Sciences. M.G lab is supported by Wellcome Trust (102696 and 206194).

Published
2019

48. Human chromosome-specific aneuploidy is influenced by DNA-dependent centromeric features

Author

Dumont, Marie, Gamba, Riccardo, Gestraud, Pierre, Klaasen, Sjoerd, Worrall, Joseph T, De Vries, Sippe G, Boudreau, Vincent, Salinas-Luypaert, Catalina, Maddox, Paul S, Lens, Susanne Ma, Kops, Geert Jpl, McClelland, Sarah E, Miga, Karen H, Fachinetti, Daniele, Dumont, Marie, Gamba, Riccardo, Gestraud, Pierre, Klaasen, Sjoerd, Worrall, Joseph T, De Vries, Sippe G, Boudreau, Vincent, Salinas-Luypaert, Catalina, Maddox, Paul S, Lens, Susanne Ma, Kops, Geert Jpl, McClelland, Sarah E, Miga, Karen H, and Fachinetti, Daniele

Abstract

Intrinsic genomic features of individual chromosomes can contribute to chromosome-specific aneuploidy. Centromeres are key elements for the maintenance of chromosome segregation fidelity via a specialized chromatin marked by CENP-A wrapped by repetitive DNA. These long stretches of repetitive DNA vary in length among human chromosomes. Using CENP-A genetic inactivation in human cells, we directly interrogate if differences in the centromere length reflect the heterogeneity of centromeric DNA-dependent features and whether this, in turn, affects the genesis of chromosome-specific aneuploidy. Using three distinct approaches, we show that mis-segregation rates vary among different chromosomes under conditions that compromise centromere function. Whole-genome sequencing and centromere mapping combined with cytogenetic analysis, small molecule inhibitors, and genetic manipulation revealed that inter-chromosomal heterogeneity of centromeric features, but not centromere length, influences chromosome segregation fidelity. We conclude that faithful chromosome segregation for most of human chromosomes is biased in favor of centromeres with high abundance of DNA-dependent centromeric components. These inter-chromosomal differences in centromere features can translate into non-random aneuploidy, a hallmark of cancer and genetic diseases.

Published
2019

49. Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen

Author

Computer Science, Menden, Michael P., Wang, Dennis, Mason, Mike J., Szalai, Bence, Bulusu, Krishna C., Guan, Yuanfang, Yu, Thomas, Kang, Jaewoo, Jeon, Minji, Wolfinger, Russ, Nguyen, Tin, Zaslavskiy, Mikhail, Jang, In Sock, Ghazoui, Zara, Ahsen, Mehmet Eren, Vogel, Robert, Neto, Elias Chaibub, Norman, Thea, Tang, Eric K. Y., Garnett, Mathew J., Di Veroli, Giovanni Y., Fawell, Stephen, Stolovitzky, Gustavo, Guinney, Justin, Dry, Jonathan R., Saez-Rodriguez, Julio, Abante, Jordi, Abecassis, Barbara Schmitz, Aben, Nanne, Aghamirzaie, Delasa, Aittokallio, Tero, Akhtari, Farida S., Al-lazikani, Bissan, Alam, Tanvir, Allam, Amin, Allen, Chad, de Almeida, Mariana Pelicano, Altarawy, Doaa, Alves, Vinicius, Amadoz, Alicia, Anchang, Benedict, Antolin, Albert A., Ash, Jeremy R., Romeo Aznar, Victoria, Ba-alawi, Wail, Bagheri, Moeen, Bajic, Vladimir, Ball, Gordon, Ballester, Pedro J., Baptista, Delora, Bare, Christopher, Bateson, Mathilde, Bender, Andreas, Bertrand, Denis, Wijayawardena, Bhagya, Boroevich, Keith A., Bosdriesz, Evert, Bougouffa, Salim, Bounova, Gergana, Brouwer, Thomas, Bryant, Barbara, Calaza, Manuel, Calderone, Alberto, Calza, Stefano, Capuzzi, Stephen, Carbonell-Caballero, Jose, Carlin, Daniel, Carter, Hannah, Castagnoli, Luisa, Celebi, Remzi, Cesareni, Gianni, Chang, Hyeokyoon, Chen, Guocai, Chen, Haoran, Chen, Huiyuan, Cheng, Lijun, Chernomoretz, Ariel, Chicco, Davide, Cho, Kwang-Hyun, Cho, Sunghwan, Choi, Daeseon, Choi, Jaejoon, Choi, Kwanghun, Choi, Minsoo, De Cock, Martine, Coker, Elizabeth, Cortes-Ciriano, Isidro, Cserzo, Miklos, Cubuk, Cankut, Curtis, Christina, Van Daele, Dries, Dang, Cuong C., Dijkstra, Tjeerd, Dopazo, Joaquin, Draghici, Sorin, Drosou, Anastasios, Dumontier, Michel, Ehrhart, Friederike, Eid, Fatma-Elzahraa, ElHefnawi, Mahmoud, Elmarakeby, Haitham A., van Engelen, Bo, Engin, Hatice Billur, de Esch, Iwan, Evelo, Chris, Falcao, Andre O., Farag, Sherif, Fernandez-Lozano, Carlos, Fisch, Kathleen, Flobak, Asmund, Fornari, Chiara, Foroushani, Amir B. K., Fotso, Donatien Chedom, Fourches, Denis, Friend, Stephen, Frigessi, Arnoldo, Gao, Feng, Gao, Xiaoting, Gerold, Jeffrey M., Gestraud, Pierre, Ghosh, Samik, Gillberg, Jussi, Godoy-Lorite, Antonia, Godynyuk, Lizzy, Godzik, Adam, Goldenberg, Anna, Gomez-Cabrero, David, Gonen, Mehmet, de Graaf, Chris, Gray, Harry, Grechkin, Maxim, Guimera, Roger, Guney, Emre, Haibe-Kains, Benjamin, Han, Younghyun, Hase, Takeshi, He, Di, He, Liye, Heath, Lenwood S., Hellton, Kristoffer H., Helmer-Citterich, Manuela, Hidalgo, Marta R., Hidru, Daniel, Hill, Steven M., Hochreiter, Sepp, Hong, Seungpyo, Hovig, Eivind, Hsueh, Ya-Chih, Hu, Zhiyuan, Huang, Justin K., Huang, R. Stephanie, Hunyady, Laszlo, Hwang, Jinseub, Hwang, Tae Hyun, Hwang, Woochang, Hwang, Yongdeuk, Isayev, Olexandr, Walk, Oliver Bear Don't, Jack, John, Jahandideh, Samad, Ji, Jiadong, Jo, Yousang, Kamola, Piotr J., Kanev, Georgi K., Karacosta, Loukia, Karimi, Mostafa, Kaski, Samuel, Kazanov, Marat, Khamis, Abdullah M., Khan, Suleiman Ali, Kiani, Narsis A., Kim, Allen, Kim, Jinhan, Kim, Juntae, Kim, Kiseong, Kim, Kyung, Kim, Sunkyu, Kim, Yongsoo, Kim, Yunseong, Kirk, Paul D. W., Kitano, Hiroaki, Klambauer, Gunter, Knowles, David, Ko, Melissa, Kohn-Luque, Alvaro, Kooistra, Albert J., Kuenemann, Melaine A., Kuiper, Martin, Kurz, Christoph, Kwon, Mijin, van Laarhoven, Twan, Laegreid, Astrid, Lederer, Simone, Lee, Heewon, Lee, Jeon, Lee, Yun Woo, Leppaho, Eemeli, Lewis, Richard, Li, Jing, Li, Lang, Liley, James, Lim, Weng Khong, Lin, Chieh, Liu, Yiyi, Lopez, Yosvany, Low, Joshua, Lysenko, Artem, Machado, Daniel, Madhukar, Neel, De Maeyer, Dries, Malpartida, Ana Belen, Mamitsuka, Hiroshi, Marabita, Francesco, Marchal, Kathleen, Marttinen, Pekka, Mason, Daniel, Mazaheri, Alireza, Mehmood, Arfa, Mehreen, Ali, Michaut, Magali, Miller, Ryan A., Mitsopoulos, Costas, Modos, Dezso, Van Moerbeke, Marijke, Moo, Keagan, Motsinger-Reif, Alison, Movva, Rajiv, Muraru, Sebastian, Muratov, Eugene, Mushthofa, Mushthofa, Nagarajan, Niranjan, Nakken, Sigve, Nath, Aritro, Neuvial, Pierre, Newton, Richard, Ning, Zheng, De Niz, Carlos, Oliva, Baldo, Olsen, Catharina, Palmeri, Antonio, Panesar, Bhawan, Papadopoulos, Stavros, Park, Jaesub, Park, Seonyeong, Park, Sungjoon, Pawitan, Yudi, Peluso, Daniele, Pendyala, Sriram, Peng, Jian, Perfetto, Livia, Pirro, Stefano, Plevritis, Sylvia, Politi, Regina, Poon, Hoifung, Porta, Eduard, Prellner, Isak, Preuer, Kristina, Angel Pujana, Miguel, Ramnarine, Ricardo, Reid, John E., Reyal, Fabien, Richardson, Sylvia, Ricketts, Camir, Rieswijk, Linda, Rocha, Miguel, Rodriguez-Gonzalvez, Carmen, Roell, Kyle, Rotroff, Daniel, de Ruiter, Julian R., Rukawa, Ploy, Sadacca, Benjamin, Safikhani, Zhaleh, Safitri, Fita, Sales-Pardo, Marta, Sauer, Sebastian, Schlichting, Moritz, Seoane, Jose A., Serra, Jordi, Shang, Ming-Mei, Sharma, Alok, Sharma, Hari, Shen, Yang, Shiga, Motoki, Shin, Moonshik, Shkedy, Ziv, Shopsowitz, Kevin, Sinai, Sam, Skola, Dylan, Smirnov, Petr, Soerensen, Izel Fourie, Soerensen, Peter, Song, Je-Hoon, Song, Sang Ok, Soufan, Othman, Spitzmueller, Andreas, Steipe, Boris, Suphavilai, Chayaporn, Tamayo, Sergio Pulido, Tamborero, David, Tang, Jing, Tanoli, Zia-ur-Rehman, Tarres-Deulofeu, Marc, Tegner, Jesper, Thommesen, Liv, Tonekaboni, Seyed Ali Madani, Tran, Hong T., De Troyer, Ewoud, Truong, Amy, Tsunoda, Tatsuhiko, Turu, Gabor, Tzeng, Guang-Yo, Verbeke, Lieven, Videla, Santiago, Vis, Daniel, Voronkov, Andrey, Votis, Konstantinos, Wang, Ashley, Wang, Hong-Qiang Horace, Wang, Po-Wei, Wang, Sheng, Wang, Wei, Wang, Xiaochen, Wang, Xin, Wennerberg, Krister, Wernisch, Lorenz, Wessels, Lodewyk, van Westen, Gerard J. P., Westerman, Bart A., White, Simon Richard, Willighagen, Egon, Wurdinger, Tom, Xie, Lei, Xie, Shuilian, Xu, Hua, Yadav, Bhagwan, Yau, Christopher, Yeerna, Huwate, Yin, Jia Wei, Yu, Michael, Yu, MinHwan, Yun, So Jeong, Zakharov, Alexey, Zamichos, Alexandros, Zanin, Massimiliano, Zeng, Li, Zenil, Hector, Zhang, Frederick, Zhang, Pengyue, Zhang, Wei, Zhao, Hongyu, Zhao, Lan, Zheng, Wenjin, Zoufir, Azedine, Zucknick, Manuela, Computer Science, Menden, Michael P., Wang, Dennis, Mason, Mike J., Szalai, Bence, Bulusu, Krishna C., Guan, Yuanfang, Yu, Thomas, Kang, Jaewoo, Jeon, Minji, Wolfinger, Russ, Nguyen, Tin, Zaslavskiy, Mikhail, Jang, In Sock, Ghazoui, Zara, Ahsen, Mehmet Eren, Vogel, Robert, Neto, Elias Chaibub, Norman, Thea, Tang, Eric K. Y., Garnett, Mathew J., Di Veroli, Giovanni Y., Fawell, Stephen, Stolovitzky, Gustavo, Guinney, Justin, Dry, Jonathan R., Saez-Rodriguez, Julio, Abante, Jordi, Abecassis, Barbara Schmitz, Aben, Nanne, Aghamirzaie, Delasa, Aittokallio, Tero, Akhtari, Farida S., Al-lazikani, Bissan, Alam, Tanvir, Allam, Amin, Allen, Chad, de Almeida, Mariana Pelicano, Altarawy, Doaa, Alves, Vinicius, Amadoz, Alicia, Anchang, Benedict, Antolin, Albert A., Ash, Jeremy R., Romeo Aznar, Victoria, Ba-alawi, Wail, Bagheri, Moeen, Bajic, Vladimir, Ball, Gordon, Ballester, Pedro J., Baptista, Delora, Bare, Christopher, Bateson, Mathilde, Bender, Andreas, Bertrand, Denis, Wijayawardena, Bhagya, Boroevich, Keith A., Bosdriesz, Evert, Bougouffa, Salim, Bounova, Gergana, Brouwer, Thomas, Bryant, Barbara, Calaza, Manuel, Calderone, Alberto, Calza, Stefano, Capuzzi, Stephen, Carbonell-Caballero, Jose, Carlin, Daniel, Carter, Hannah, Castagnoli, Luisa, Celebi, Remzi, Cesareni, Gianni, Chang, Hyeokyoon, Chen, Guocai, Chen, Haoran, Chen, Huiyuan, Cheng, Lijun, Chernomoretz, Ariel, Chicco, Davide, Cho, Kwang-Hyun, Cho, Sunghwan, Choi, Daeseon, Choi, Jaejoon, Choi, Kwanghun, Choi, Minsoo, De Cock, Martine, Coker, Elizabeth, Cortes-Ciriano, Isidro, Cserzo, Miklos, Cubuk, Cankut, Curtis, Christina, Van Daele, Dries, Dang, Cuong C., Dijkstra, Tjeerd, Dopazo, Joaquin, Draghici, Sorin, Drosou, Anastasios, Dumontier, Michel, Ehrhart, Friederike, Eid, Fatma-Elzahraa, ElHefnawi, Mahmoud, Elmarakeby, Haitham A., van Engelen, Bo, Engin, Hatice Billur, de Esch, Iwan, Evelo, Chris, Falcao, Andre O., Farag, Sherif, Fernandez-Lozano, Carlos, Fisch, Kathleen, Flobak, Asmund, Fornari, Chiara, Foroushani, Amir B. K., Fotso, Donatien Chedom, Fourches, Denis, Friend, Stephen, Frigessi, Arnoldo, Gao, Feng, Gao, Xiaoting, Gerold, Jeffrey M., Gestraud, Pierre, Ghosh, Samik, Gillberg, Jussi, Godoy-Lorite, Antonia, Godynyuk, Lizzy, Godzik, Adam, Goldenberg, Anna, Gomez-Cabrero, David, Gonen, Mehmet, de Graaf, Chris, Gray, Harry, Grechkin, Maxim, Guimera, Roger, Guney, Emre, Haibe-Kains, Benjamin, Han, Younghyun, Hase, Takeshi, He, Di, He, Liye, Heath, Lenwood S., Hellton, Kristoffer H., Helmer-Citterich, Manuela, Hidalgo, Marta R., Hidru, Daniel, Hill, Steven M., Hochreiter, Sepp, Hong, Seungpyo, Hovig, Eivind, Hsueh, Ya-Chih, Hu, Zhiyuan, Huang, Justin K., Huang, R. Stephanie, Hunyady, Laszlo, Hwang, Jinseub, Hwang, Tae Hyun, Hwang, Woochang, Hwang, Yongdeuk, Isayev, Olexandr, Walk, Oliver Bear Don't, Jack, John, Jahandideh, Samad, Ji, Jiadong, Jo, Yousang, Kamola, Piotr J., Kanev, Georgi K., Karacosta, Loukia, Karimi, Mostafa, Kaski, Samuel, Kazanov, Marat, Khamis, Abdullah M., Khan, Suleiman Ali, Kiani, Narsis A., Kim, Allen, Kim, Jinhan, Kim, Juntae, Kim, Kiseong, Kim, Kyung, Kim, Sunkyu, Kim, Yongsoo, Kim, Yunseong, Kirk, Paul D. W., Kitano, Hiroaki, Klambauer, Gunter, Knowles, David, Ko, Melissa, Kohn-Luque, Alvaro, Kooistra, Albert J., Kuenemann, Melaine A., Kuiper, Martin, Kurz, Christoph, Kwon, Mijin, van Laarhoven, Twan, Laegreid, Astrid, Lederer, Simone, Lee, Heewon, Lee, Jeon, Lee, Yun Woo, Leppaho, Eemeli, Lewis, Richard, Li, Jing, Li, Lang, Liley, James, Lim, Weng Khong, Lin, Chieh, Liu, Yiyi, Lopez, Yosvany, Low, Joshua, Lysenko, Artem, Machado, Daniel, Madhukar, Neel, De Maeyer, Dries, Malpartida, Ana Belen, Mamitsuka, Hiroshi, Marabita, Francesco, Marchal, Kathleen, Marttinen, Pekka, Mason, Daniel, Mazaheri, Alireza, Mehmood, Arfa, Mehreen, Ali, Michaut, Magali, Miller, Ryan A., Mitsopoulos, Costas, Modos, Dezso, Van Moerbeke, Marijke, Moo, Keagan, Motsinger-Reif, Alison, Movva, Rajiv, Muraru, Sebastian, Muratov, Eugene, Mushthofa, Mushthofa, Nagarajan, Niranjan, Nakken, Sigve, Nath, Aritro, Neuvial, Pierre, Newton, Richard, Ning, Zheng, De Niz, Carlos, Oliva, Baldo, Olsen, Catharina, Palmeri, Antonio, Panesar, Bhawan, Papadopoulos, Stavros, Park, Jaesub, Park, Seonyeong, Park, Sungjoon, Pawitan, Yudi, Peluso, Daniele, Pendyala, Sriram, Peng, Jian, Perfetto, Livia, Pirro, Stefano, Plevritis, Sylvia, Politi, Regina, Poon, Hoifung, Porta, Eduard, Prellner, Isak, Preuer, Kristina, Angel Pujana, Miguel, Ramnarine, Ricardo, Reid, John E., Reyal, Fabien, Richardson, Sylvia, Ricketts, Camir, Rieswijk, Linda, Rocha, Miguel, Rodriguez-Gonzalvez, Carmen, Roell, Kyle, Rotroff, Daniel, de Ruiter, Julian R., Rukawa, Ploy, Sadacca, Benjamin, Safikhani, Zhaleh, Safitri, Fita, Sales-Pardo, Marta, Sauer, Sebastian, Schlichting, Moritz, Seoane, Jose A., Serra, Jordi, Shang, Ming-Mei, Sharma, Alok, Sharma, Hari, Shen, Yang, Shiga, Motoki, Shin, Moonshik, Shkedy, Ziv, Shopsowitz, Kevin, Sinai, Sam, Skola, Dylan, Smirnov, Petr, Soerensen, Izel Fourie, Soerensen, Peter, Song, Je-Hoon, Song, Sang Ok, Soufan, Othman, Spitzmueller, Andreas, Steipe, Boris, Suphavilai, Chayaporn, Tamayo, Sergio Pulido, Tamborero, David, Tang, Jing, Tanoli, Zia-ur-Rehman, Tarres-Deulofeu, Marc, Tegner, Jesper, Thommesen, Liv, Tonekaboni, Seyed Ali Madani, Tran, Hong T., De Troyer, Ewoud, Truong, Amy, Tsunoda, Tatsuhiko, Turu, Gabor, Tzeng, Guang-Yo, Verbeke, Lieven, Videla, Santiago, Vis, Daniel, Voronkov, Andrey, Votis, Konstantinos, Wang, Ashley, Wang, Hong-Qiang Horace, Wang, Po-Wei, Wang, Sheng, Wang, Wei, Wang, Xiaochen, Wang, Xin, Wennerberg, Krister, Wernisch, Lorenz, Wessels, Lodewyk, van Westen, Gerard J. P., Westerman, Bart A., White, Simon Richard, Willighagen, Egon, Wurdinger, Tom, Xie, Lei, Xie, Shuilian, Xu, Hua, Yadav, Bhagwan, Yau, Christopher, Yeerna, Huwate, Yin, Jia Wei, Yu, Michael, Yu, MinHwan, Yun, So Jeong, Zakharov, Alexey, Zamichos, Alexandros, Zanin, Massimiliano, Zeng, Li, Zenil, Hector, Zhang, Frederick, Zhang, Pengyue, Zhang, Wei, Zhao, Hongyu, Zhao, Lan, Zheng, Wenjin, Zoufir, Azedine, and Zucknick, Manuela

Abstract

The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca's large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells.

Published
2019

50. New insight for pharmacogenomics studies from the transcriptional analysis of two large-scale cancer cell line panels (vol 7, 15126, 2016)

Author

Sadacca, Benjamin, Hamy, Anne-Sophie, Laurent, C., Gestraud, Pierre, Bonsang-Kitzis, Hélène, Pinheiro, Alice, Abecassis, Judith, Neuvial, Pierre, Reyal, Fabien, Residual Tumor & Response to Treatment Laboratory (RT2Lab) - Translational Research Department, Institut Curie, Immunité et cancer (U932), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université d'Évry-Val-d'Essonne (UEVE), Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Surgery, Institut Curie [Paris], Université Paris sciences et lettres (PSL), Laboratoire de Mathématiques et Modélisation d'Evry (LaMME), Institut National de la Recherche Agronomique (INRA)-Université d'Évry-Val-d'Essonne (UEVE)-ENSIIE-Centre National de la Recherche Scientifique (CNRS), Institut de Mathématiques de Toulouse UMR5219 (IMT), Université Toulouse Capitole (UT Capitole), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées (INSA)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), ProdInra, Migration, Institut Curie [Paris]-MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse 1 Capitole (UT1), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), and Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], education
Abstract

Author Correction: New insight for pharmacogenomics studies from the transcriptional analysis of two large-scale cancer cell line panels; International audience

Published
2018

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