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120 results on '"Amzallag, Arnaud"'

1. A landscape of response to drug combinations in non-small cell lung cancer

Author

Nair, Nishanth Ulhas, Greninger, Patricia, Zhang, Xiaohu, Friedman, Adam A., Amzallag, Arnaud, Cortez, Eliane, Sahu, Avinash Das, Lee, Joo Sang, Dastur, Anahita, Egan, Regina K., Murchie, Ellen, Ceribelli, Michele, Crowther, Giovanna S., Beck, Erin, McClanaghan, Joseph, Klump-Thomas, Carleen, Boisvert, Jessica L., Damon, Leah J., Wilson, Kelli M., Ho, Jeffrey, Tam, Angela, McKnight, Crystal, Michael, Sam, Itkin, Zina, Garnett, Mathew J., Engelman, Jeffrey A., Haber, Daniel A., Thomas, Craig J., Ruppin, Eytan, and Benes, Cyril H.

Published
2023
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2. Genome-wide prediction of synthetic rescue mediators of resistance to targeted and immunotherapy.

Author

Sahu, Avinash, S Lee, Joo, Wang, Zhiyong, Zhang, Gao, Iglesias-Bartolome, Ramiro, Tian, Tian, Wei, Zhi, Miao, Benchun, Nair, Nishanth, Ponomarova, Olga, Friedman, Adam, Amzallag, Arnaud, Moll, Tabea, Kasumova, Gyulnara, Greninger, Patricia, Egan, Regina, Damon, Leah, Frederick, Dennie, Jerby-Arnon, Livnat, Wagner, Allon, Cheng, Kuoyuan, Park, Seung, Robinson, Welles, Gardner, Kevin, Boland, Genevieve, Hannenhalli, Sridhar, Herlyn, Meenhard, Benes, Cyril, Flaherty, Keith, Luo, Ji, Gutkind, J, and Ruppin, Eytan

Subjects
drug combination, drug resistance, immunotherapy, synergy, Computational Biology, Drug Resistance, Neoplasm, Drug Synergism, Female, Gene Expression Profiling, Humans, Immunotherapy, Male, Melanoma, Molecular Targeted Therapy, Synthetic Lethal Mutations
Abstract

Most patients with advanced cancer eventually acquire resistance to targeted therapies, spurring extensive efforts to identify molecular events mediating therapy resistance. Many of these events involve synthetic rescue (SR) interactions, where the reduction in cancer cell viability caused by targeted gene inactivation is rescued by an adaptive alteration of another gene (the rescuer). Here, we perform a genome-wide in silico prediction of SR rescuer genes by analyzing tumor transcriptomics and survival data of 10,000 TCGA cancer patients. Predicted SR interactions are validated in new experimental screens. We show that SR interactions can successfully predict cancer patients response and emerging resistance. Inhibiting predicted rescuer genes sensitizes resistant cancer cells to therapies synergistically, providing initial leads for developing combinatorial approaches to overcome resistance proactively. Finally, we show that the SR analysis of melanoma patients successfully identifies known mediators of resistance to immunotherapy and predicts novel rescuers.

Published
2019

3. Differential Effector Engagement by Oncogenic KRAS

Author

Yuan, Tina L, Amzallag, Arnaud, Bagni, Rachel, Yi, Ming, Afghani, Shervin, Burgan, William, Fer, Nicole, Strathern, Leslie A, Powell, Katie, Smith, Brian, Waters, Andrew M, Drubin, David, Thomson, Ty, Liao, Rosy, Greninger, Patricia, Stein, Giovanna T, Murchie, Ellen, Cortez, Eliane, Egan, Regina K, Procter, Lauren, Bess, Matthew, Cheng, Kwong Tai, Lee, Chih-Shia, Lee, Liam Changwoo, Fellmann, Christof, Stephens, Robert, Luo, Ji, Lowe, Scott W, Benes, Cyril H, and McCormick, Frank

Subjects
Biochemistry and Cell Biology, Biological Sciences, Lung, Cancer, AMP-Activated Protein Kinase Kinases, Adenylate Kinase, Cell Line, Tumor, Drug Evaluation, Preclinical, Gene Expression Regulation, Neoplastic, Humans, Metabolic Networks and Pathways, Models, Biological, Mutation, Oncogenes, Protein Serine-Threonine Kinases, Proto-Oncogene Proteins p21(ras), RNA Interference, RNA, Small Interfering, Small Molecule Libraries, KRAS, RNAi screen, RSK, paralogs, redundancy, Medical Physiology, Biological sciences
Abstract

KRAS can bind numerous effector proteins, which activate different downstream signaling events. The best known are RAF, phosphatidylinositide (PI)-3' kinase, and RalGDS families, but many additional direct and indirect effectors have been reported. We have assessed how these effectors contribute to several major phenotypes in a quantitative way, using an arrayed combinatorial siRNA screen in which we knocked down 41 KRAS effectors nodes in 92 cell lines. We show that every cell line has a unique combination of effector dependencies, but in spite of this heterogeneity, we were able to identify two major subtypes of KRAS mutant cancers of the lung, pancreas, and large intestine, which reflect different KRAS effector engagement and opportunities for therapeutic intervention.

Published
2018

5. P459: DISEASE MONITORING OF NPM1-MUTANT (MUT) ACUTE MYELOID LEUKEMIA (AML) USING MEASURABLE RESIDUAL DISEASE (MRD) ASSESSMENTS DURING ORAL AZACITIDINE (ORAL-AZA) TREATMENT (TX): A QUAZAR AML-001 SUBANALYSIS

Author

Lopes De Menezes, Daniel, primary, Roboz, Gail, additional, Döhner, Hartmut, additional, Wei, Andrew, additional, Teresa Voso, Maria, additional, Schuh, Andre, additional, See, Wendy L., additional, Ugidos, Manuel, additional, Amzallag, Arnaud, additional, Risueño, Alberto, additional, H. Eng, Kevin, additional, Nvs Suragani, Rajasekhar, additional, Skikne, Barry, additional, Beach, CL, additional, Prebet, Thomas, additional, and Gandhi, Anita, additional

Published
2023
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6. P411: LONGITUDINAL CHARACTERIZATION OF MOLECULAR VARIANTS AT REMISSION AND RELAPSE: SUBANALYSIS OF THE QUAZAR AML-001 TRIAL

Author

Lopes De Menezes, Daniel, primary, Wei, Andrew, additional, Döhner, Hartmut, additional, Roboz, Gail, additional, Teresa Voso, Maria, additional, Schuh, Andre, additional, See, Wendy L., additional, Ugidos, Manuel, additional, Amzallag, Arnaud, additional, Risueño, Alberto, additional, Kyriakopoulos, Charalampos, additional, Nvs Suragani, Rajasekhar, additional, Skikne, Barry, additional, Beach, CL, additional, Prebet, Thomas, additional, and Gandhi, Anita, additional

Published
2023
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7. Cell line information from Preclinical Anticancer Efficacy of BET Bromodomain Inhibitors Is Determined by the Apoptotic Response

Author

Conery, Andrew R., primary, Centore, Richard C., primary, Spillane, Kerry L., primary, Follmer, Nicole E., primary, Bommi-Reddy, Archana, primary, Hatton, Charlie, primary, Bryant, Barbara M., primary, Greninger, Patricia, primary, Amzallag, Arnaud, primary, Benes, Cyril H., primary, Mertz, Jennifer A., primary, and Sims, Robert J., primary

Published
2023
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8. Supplementary figures from Preclinical Anticancer Efficacy of BET Bromodomain Inhibitors Is Determined by the Apoptotic Response

Author

Conery, Andrew R., primary, Centore, Richard C., primary, Spillane, Kerry L., primary, Follmer, Nicole E., primary, Bommi-Reddy, Archana, primary, Hatton, Charlie, primary, Bryant, Barbara M., primary, Greninger, Patricia, primary, Amzallag, Arnaud, primary, Benes, Cyril H., primary, Mertz, Jennifer A., primary, and Sims, Robert J., primary

Published
2023
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9. Supporting data Fig 3A, 3B, 4D, S6 from Preclinical Anticancer Efficacy of BET Bromodomain Inhibitors Is Determined by the Apoptotic Response

Author

Conery, Andrew R., primary, Centore, Richard C., primary, Spillane, Kerry L., primary, Follmer, Nicole E., primary, Bommi-Reddy, Archana, primary, Hatton, Charlie, primary, Bryant, Barbara M., primary, Greninger, Patricia, primary, Amzallag, Arnaud, primary, Benes, Cyril H., primary, Mertz, Jennifer A., primary, and Sims, Robert J., primary

Published
2023
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10. Supplementary Materials and Methods from Preclinical Anticancer Efficacy of BET Bromodomain Inhibitors Is Determined by the Apoptotic Response

Author

Conery, Andrew R., primary, Centore, Richard C., primary, Spillane, Kerry L., primary, Follmer, Nicole E., primary, Bommi-Reddy, Archana, primary, Hatton, Charlie, primary, Bryant, Barbara M., primary, Greninger, Patricia, primary, Amzallag, Arnaud, primary, Benes, Cyril H., primary, Mertz, Jennifer A., primary, and Sims, Robert J., primary

Published
2023
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11. Supplementary tables from Preclinical Anticancer Efficacy of BET Bromodomain Inhibitors Is Determined by the Apoptotic Response

Author

Conery, Andrew R., primary, Centore, Richard C., primary, Spillane, Kerry L., primary, Follmer, Nicole E., primary, Bommi-Reddy, Archana, primary, Hatton, Charlie, primary, Bryant, Barbara M., primary, Greninger, Patricia, primary, Amzallag, Arnaud, primary, Benes, Cyril H., primary, Mertz, Jennifer A., primary, and Sims, Robert J., primary

Published
2023
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12. Data from Preclinical Anticancer Efficacy of BET Bromodomain Inhibitors Is Determined by the Apoptotic Response

Author

Conery, Andrew R., primary, Centore, Richard C., primary, Spillane, Kerry L., primary, Follmer, Nicole E., primary, Bommi-Reddy, Archana, primary, Hatton, Charlie, primary, Bryant, Barbara M., primary, Greninger, Patricia, primary, Amzallag, Arnaud, primary, Benes, Cyril H., primary, Mertz, Jennifer A., primary, and Sims, Robert J., primary

Published
2023
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14. Patient-derived models of acquired resistance can identify effective drug combinations for cancer

Author

Crystal, Adam S., Shaw, Alice T., Sequist, Lecia V., Friboulet, Luc, Niederst, Matthew J., Lockerman, Elizabeth L., Frias, Rosa L., Gainor, Justin F., Amzallag, Arnaud, Greninger, Patricia, Lee, Dana, Kalsy, Anuj, Gomez-Caraballo, Maria, Elamine, Leila, Howe, Emily, Hur, Wooyoung, Lifshits, Eugene, Robinson, Hayley E., Katayama, Ryohei, Faber, Anthony C., Awad, Mark M., Ramaswamy, Sridhar, Mino-Kenudson, Mari, Iafrate, A. John, Benes, Cyril H., and Engelman, Jeffrey A.

Published
2014

15. 1277 Identification of clinically relevant spatial tissue phenotypes in large-scale multiplex immunofluorescence data via unsupervised graph learning in non-small cell lung cancer

Author

Egger, Robert, primary, Fisher, Andrew, additional, Drage, Michael, additional, Trillo-Tinoco, Jimena, additional, Abel, John, additional, Browne, Andrew, additional, Rajan, Deepta, additional, Wang, Tai, additional, Conway, Jake, additional, King, Catherine, additional, Brosnan-Cashman, Jacqueline, additional, Lewin, Anne, additional, Amzallag, Arnaud, additional, Lila, Thomas, additional, Simpson, Tyler, additional, Montalto, Mike, additional, Chen, Benjamin, additional, Glass, Benjamin, additional, and Baxi, Vipul, additional

Published
2022
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16. Targeting transcription regulation in cancer with a covalent CDK7 inhibitor

Author

Kwiatkowski, Nicholas, Zhang, Tinghu, Rahl, Peter B., Abraham, Brian J., Reddy, Jessica, Ficarro, Scott B., Dastur, Anahita, Amzallag, Arnaud, Ramaswamy, Sridhar, Tesar, Bethany, Jenkins, Catherine E., Hannett, Nancy M., McMillin, Douglas, Sanda, Takaomi, Sim, Taebo, Kim, Nam Doo, Look, Thomas, Mitsiades, Constantine S., Weng, Andrew P., Brown, Jennifer R., Benes, Cyril H., Marto, Jarrod A., Young, Richard A., and Gray, Nathanael S.

Subjects
Pharmacology -- Analysis, Cancer -- Research -- Genetic aspects -- Care and treatment, Genetic regulation -- Analysis, Genetic transcription -- Analysis, Transcription factors -- Research, Cysteine -- Analysis -- Health aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Tumour oncogenes include transcription factors that co-opt the general transcriptional machinery to sustain the oncogenic state (1), but direct pharmacological inhibition of transcription factors has so far proven difficult (2). However, the transcriptional machinery contains various enzymatic cofactors that can be targeted for the development of new therapeutic candidates (3), including cyclin-dependent kinases (CDKs) (4). Here we present the discovery and characterization of a covalent CDK7 inhibitor, THZ1, which has the unprecedented ability to target a remote cysteine residue located outside of the canonical kinase domain, providing an unanticipated means of achieving selectivity for CDK7. Cancer cell-line profiling indicates that a subset of cancer cell lines, including human T-cell acute lymphoblastic leukaemia (T-ALL), have exceptional sensitivity to THZ1. Genome-wide analysis in Jurkat T-ALL cells shows that THZ1 disproportionally affects transcription of RUNX1 and suggests that sensitivity to THZ1 may be due to vulnerability conferred by the RUNX1 super-enhancer and the key role of RUNX1 in the core transcriptional regulatory circuitry of these tumour cells. Pharmacological modulation of CDK7 kinase activity may thus provide an approach to identify and treat tumour types that are dependent on transcription for maintenance of the oncogenic state., In an effort to discover new inhibitors of kinases that regulate gene transcription, we performed cell-based screening and kinase selectivity profiling of a library of known and novel ATP-site-directed kinase [...]

Published
2014

17. Pharmacogenomic agreement between two cancer cell line data sets

Author

Stransky, Nicolas, Ghandi, Mahmoud, Kryukov, Gregory V., Garraway, Levi A., Lehár, Joseph, Liu, Manway, Sonkin, Dmitriy, Kauffmann, Audrey, Venkatesan, Kavitha, Edelman, Elena J., Riester, Markus, Barretina, Jordi, Caponigro, Giordano, Schlegel, Robert, Sellers, William R., Stegmeier, Frank, Morrissey, Michael, Amzallag, Arnaud, Pruteanu-Malinici, Iulian, Haber, Daniel A., Ramaswamy, Sridhar, Benes, Cyril H., Menden, Michael P., Iorio, Francesco, Stratton, Michael R., McDermott, Ultan, Garnett, Mathew J., and Saez-Rodriguez, Julio

Published
2015
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18. CANCER THERAPY: Patient-derived models of acquired resistance can identify effective drug combinations for cancer

Author

Crystal, Adam S., Shaw, Alice T., Sequist, Lecia V., Friboulet, Luc, Niederst, Matthew J., Lockerman, Elizabeth L., Frias, Rosa L., Gainor, Justin F., Amzallag, Arnaud, Greninger, Patricia, Lee, Dana, Kalsy, Anuj, Gomez-Caraballo, Maria, Elamine, Leila, Howe, Emily, Hur, Wooyoung, Lifshits, Eugene, Robinson, Hayley E., Katayama, Ryohei, Faber, Anthony C., Awad, Mark M., Ramaswamy, Sridhar, Mino-Kenudson, Mari, Iafrate, John A., Benes, Cyril H., and Engelman, Jeffrey A.

Published
2014
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19. A landscape of synergistic drug combinations in non-small-cell lung cancer

Author

Nair, Nishanth Ulhas, primary, Greninger, Patricia, additional, Friedman, Adam, additional, Amzallag, Arnaud, additional, Cortez, Eliane, additional, Sahu, Avinash Das, additional, Lee, Joo Sang, additional, Dastur, Anahita, additional, Egan, Regina K., additional, Murchie, Ellen, additional, Crowther, Giovanna Stein, additional, McClanaghan, Joseph, additional, Boisvert, Jessica, additional, Damon, Leah, additional, Ho, Jeffrey, additional, Tam, Angela, additional, Garnett, Mathew J, additional, Engelman, Jeffrey A., additional, Haber, Daniel A., additional, Ruppin, Eytan, additional, and Benes, Cyril H., additional

Published
2021
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21. Clonal Dynamics of Gene Mutations during Oral Azacitidine Maintenance Therapy in Patients with Acute Myeloid Leukemia (AML): Outcomes from the QUAZAR AML-001 Trial

Author

Lopes De Menezes, Daniel, Guerrero, Manuel Ugidos, Amzallag, Arnaud, See, Wendy L., Risueno, Alberto, Kyriakopoulos, Charalampos, Suragani, Rajasekhar N.V.S., Skikne, Barry S., Beach, C.L., Prebet, Thomas, Voso, Maria Teresa, Schuh, Andre C., Roboz, Gail J., Döhner, Hartmut, Wei, Andrew H., and Gandhi, Anita K.

Published
2023
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25. Correction: Landscape of Targeted Anti-Cancer Drug Synergies in Melanoma Identifies a Novel BRAF-VEGFR/PDGFR Combination Treatment.

Author

Friedman, Adam A., Amzallag, Arnaud, Pruteanu-Malinici, Iulian, Baniya, Subash, Cooper, Zachary A., Piris, Adriano, Hargreaves, Leeza, Igras, Vivien, Frederick, Dennie T., Lawrence, Donald P., Haber, Daniel A., Flaherty, Keith T., Wargo, Jennifer A., Ramaswamy, Sridhar, Benes, Cyril H., and Fisher, David E.

Subjects
*DRUG synergism, *ANTINEOPLASTIC agents, *MELANOMA
Abstract

There is an error in S3 Table. Some data in the columns are duplicated. Please view the correct S3 Table below.Supporting informationS3 Table(XLSX)By Adam A. Friedman; Arnaud Amzallag; Iulian Pruteanu-Malinici; Subash Baniya; Zachary A. Cooper; Adriano Piris; Leeza Hargreaves; Vivien Igras; Dennie T. Frederick; Donald P. Lawrence; Daniel A. Haber; Keith T. Flaherty; Jennifer A. Wargo; Sridhar Ramaswamy; Cyril H. Benes and David E. FisherReported by Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author [Extracted from the article]

Published
2024
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28. Abstract LB-149: Genome-wide prediction of synthetic rescue mediators of resistance to targeted and immunotherapy

Author

Das, Avinash, primary, Lee, Joo Sang, additional, Zhang, Gao, additional, Wang, Zhiyong, additional, Amzallag, Arnaud, additional, Boland, Genevieve, additional, Hannenhalli, Sridhar, additional, Herlyn, Meenhard, additional, Benes, Cyril, additional, Gutkind, J. Silvio, additional, Flaherty, Keity, additional, and Ruppin, Eytan, additional

Published
2019
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29. Probabilistic base calling of Solexa sequencing data

Author

Iseli Christian, Amzallag Arnaud, Rougemont Jacques, Farinelli Laurent, Xenarios Ioannis, and Naef Felix

Subjects
Computer applications to medicine. Medical informatics, R858-859.7, Biology (General), QH301-705.5
Abstract

Abstract Background Solexa/Illumina short-read ultra-high throughput DNA sequencing technology produces millions of short tags (up to 36 bases) by parallel sequencing-by-synthesis of DNA colonies. The processing and statistical analysis of such high-throughput data poses new challenges; currently a fair proportion of the tags are routinely discarded due to an inability to match them to a reference sequence, thereby reducing the effective throughput of the technology. Results We propose a novel base calling algorithm using model-based clustering and probability theory to identify ambiguous bases and code them with IUPAC symbols. We also select optimal sub-tags using a score based on information content to remove uncertain bases towards the ends of the reads. Conclusion We show that the method improves genome coverage and number of usable tags as compared with Solexa's data processing pipeline by an average of 15%. An R package is provided which allows fast and accurate base calling of Solexa's fluorescence intensity files and the production of informative diagnostic plots.

Published
2008
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30. Harnessing synthetic lethality to predict the response to cancer treatment

Author

Lee, Joo Sang, primary, Das, Avinash, additional, Jerby-Arnon, Livnat, additional, Arafeh, Rand, additional, Auslander, Noam, additional, Davidson, Matthew, additional, McGarry, Lynn, additional, James, Daniel, additional, Amzallag, Arnaud, additional, Park, Seung Gu, additional, Cheng, Kuoyuan, additional, Robinson, Welles, additional, Atias, Dikla, additional, Stossel, Chani, additional, Buzhor, Ella, additional, Stein, Gidi, additional, Waterfall, Joshua J., additional, Meltzer, Paul S., additional, Golan, Talia, additional, Hannenhalli, Sridhar, additional, Gottlieb, Eyal, additional, Benes, Cyril H., additional, Samuels, Yardena, additional, Shanks, Emma, additional, and Ruppin, Eytan, additional

Published
2018
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31. Genome-wide prediction of synthetic rescue mediators of resistance to targeted and immunotherapy

Author

Das, Avinash, primary, Lee, Joo Sang, additional, Zhang, Gao, additional, Wang, Zhiyong, additional, Iglesias-Bartolome, Ramiro, additional, Tian, Tian, additional, Wei, Zhi, additional, Miao, Benchun, additional, Nair, Nishanth Ulhas, additional, Ponomarova, Olga, additional, Friedman, Adam A., additional, Amzallag, Arnaud, additional, Moll, Tabea, additional, Kasumova, Gyulnara, additional, Greninger, Patricia, additional, Egan, Regina K., additional, Damon, Leah J., additional, Frederick, Dennie T., additional, Wagner, Allon, additional, Cheng, Kuoyuan, additional, Park, Seung Gu, additional, Robinson, Welles, additional, Gardner, Kevin, additional, Boland, Genevieve, additional, Hannenhalli, Sridhar, additional, Herlyn, Meenhard, additional, Benes, Cyril, additional, Gutkind, J. Silvio, additional, Flaherty, Keith, additional, and Ruppin, Eytan, additional

Published
2018
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32. Abstract A188: Harnessing synthetic lethality to predict the response to cancer treatments

Author

Lee, Joo S., primary, Das, Avinash, additional, Jerby-Arnon, Livnat, additional, Arafeh, Rand, additional, Davidson, Matthew, additional, Amzallag, Arnaud, additional, Park, Seung Gu, additional, Cheng, Kuoyuan, additional, Robinson, Welles, additional, Atias, Dikla, additional, Stossel, Chani, additional, Buzhor, Ella, additional, Stein, Gidi, additional, Waterfall, Joshua J., additional, Meltzer, Paul S., additional, Golan, Talia, additional, Hannenhalli, Sridhar, additional, Gottlieb, Eyal, additional, Benes, Cyril H., additional, Samuels, Yardena, additional, Shanks, Emma, additional, and Ruppin, Eytan, additional

Published
2018
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34. Bending modes of DNA directly addressed by cryo-electron microscopy of DNA minicircles

Author

Demurtas, Davide, Amzallag, Arnaud, Rawdon, Eric J., Maddocks, John H., Dubochet, Jacques, Stasiak, Andrzej, Demurtas, Davide, Amzallag, Arnaud, Rawdon, Eric J., Maddocks, John H., Dubochet, Jacques, and Stasiak, Andrzej

Abstract

We use cryo-electron microscopy (cryo-EM) to study the 3D shapes of 94-bp-long DNA minicircles and address the question of whether cyclization of such short DNA molecules necessitates the formation of sharp, localized kinks in DNA or whether the necessary bending can be redistributed and accomplished within the limits of the elastic, standard model of DNA flexibility. By comparing the shapes of covalently closed, nicked and gapped DNA minicircles, we conclude that 94-bp-long covalently closed and nicked DNA minicircles do not show sharp kinks while gapped DNA molecules, containing very flexible single-stranded regions, do show sharp kinks. We corroborate the results of cryo-EM studies by using Bal31 nuclease to probe for the existence of kinks in 94-bp-long minicircles

Published
2017

37. Abstract 543: Harnessing synthetic lethality to predict clinical outcomes of cancer treatment

Author

Lee, Joo Sang, primary, Das, Avinash, additional, Jerby-Arnon, Livnat, additional, Park, Seung Gu, additional, Davidson, Matthew, additional, Atias, Dikla, additional, Amzallag, Arnaud, additional, Stossel, Chani, additional, Buzhor, Ella, additional, Robinson, Welles, additional, Cheng, Kuoyuan, additional, Waterfall, Joshua J., additional, Meltzer, Paul S., additional, Hannenhalli, Sridhar, additional, Benes, Cyril H., additional, Golan, Talia, additional, Shanks, Emma, additional, and Ruppin, Eytan, additional

Published
2017
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38. Abstract B19: Targeting dependencies within apoptotic pathways through inhibition of BET bromodomains

Author

Conery, Andrew R., primary, Centore, Richard C., additional, Spillane, Kerry L., additional, Follmer, Nicole E., additional, Bommi-Reddy, Archana, additional, Hatton, Charlie, additional, Bryant, Barbara M., additional, Greninger, Patricia, additional, Amzallag, Arnaud, additional, Benes, Cyril H., additional, Mertz, Jennifer A., additional, and Sims, Robert J., additional

Published
2017
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39. Consistency of drug profiles and predictors in large-scale cancer cell line data

Author

Stransky, Nicolas, Ghandi, Mahmoud, Kryukov, Gregory V., Garraway, Levi A., Amzallag, Arnaud, Pruteanu-Malinici, Iulian, Haber, Daniel A., Ramaswamy, Sridhar, Benes, Cyril H., Lehár, Joseph, Liu, Manway, Sonkin, Dmitriy, Kauffmann, Audrey, Venkatesan, Kavitha, Edelman, Elena J., Riester, Markus, Barretina, Jordi, Caponigro, Giordano, Schlegel, Robert, Sellers, William, Stegmeier, Frank, Morrissey, Michael, Menden, Michael P., Iorio, Francesco, Stratton, Michael R., McDermott, Ultan, Saez-Rodriguez, Julio, and Garnett, Mathew J.

Subjects
Inhibitory Concentration 50, Databases, Factual, Pharmacogenetics, Cell Line, Tumor, Neoplasms, Datasets as Topic, Humans, Reproducibility of Results, Article
Abstract

Large cancer cell line collections broadly capture the genomic diversity of human cancers and provide valuable insight into anti-cancer drug response. Here we show substantial agreement and biological consilience between drug sensitivity measurements and their associated genomic predictors from two publicly available large-scale pharmacogenomics resources: The Cancer Cell Line Encyclopedia and the Genomics of Drug Sensitivity in Cancer databases.

Published
2015

40. Preclinical Anticancer Efficacy of BET Bromodomain Inhibitors Is Determined by the Apoptotic Response

Author

Conery, Andrew R., primary, Centore, Richard C., additional, Spillane, Kerry L., additional, Follmer, Nicole E., additional, Bommi-Reddy, Archana, additional, Hatton, Charlie, additional, Bryant, Barbara M., additional, Greninger, Patricia, additional, Amzallag, Arnaud, additional, Benes, Cyril H., additional, Mertz, Jennifer A., additional, and Sims, Robert J., additional

Published
2016
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41. Targeting transcription regulation in cancer with a covalent CDK7 inhibitor

Author

Massachusetts Institute of Technology. Department of Biology, Whitehead Institute for Biomedical Research, Reddy, Jessica, Young, Richard A., Kwiatkowski, Nicholas P., Zhang, Tinghu, Rahl, Peter B., Abraham, Brian J., Ficarro, Scott B., Dastur, Anahita, Amzallag, Arnaud, Ramaswamy, Sridhar, Tesar, Bethany, Jenkins, Catherine E., Hannett, Nancy M., McMillin, Douglas, Sanda, Takaomi, Sim, Taebo, Kim, Nam Doo, Look, A. Thomas, Mitsiades, Constantine S., Weng, Andrew P., Brown, Jennifer R., Benes, Cyril H., Marto, Jarrod A., Gray, Nathanael S., Massachusetts Institute of Technology. Department of Biology, Whitehead Institute for Biomedical Research, Reddy, Jessica, Young, Richard A., Kwiatkowski, Nicholas P., Zhang, Tinghu, Rahl, Peter B., Abraham, Brian J., Ficarro, Scott B., Dastur, Anahita, Amzallag, Arnaud, Ramaswamy, Sridhar, Tesar, Bethany, Jenkins, Catherine E., Hannett, Nancy M., McMillin, Douglas, Sanda, Takaomi, Sim, Taebo, Kim, Nam Doo, Look, A. Thomas, Mitsiades, Constantine S., Weng, Andrew P., Brown, Jennifer R., Benes, Cyril H., Marto, Jarrod A., and Gray, Nathanael S.

Abstract

Tumour oncogenes include transcription factors that co-opt the general transcriptional machinery to sustain the oncogenic state, but direct pharmacological inhibition of transcription factors has so far proven difficult. However, the transcriptional machinery contains various enzymatic cofactors that can be targeted for the development of new therapeutic candidates, including cyclin-dependent kinases (CDKs). Here we present the discovery and characterization of a covalent CDK7 inhibitor, THZ1, which has the unprecedented ability to target a remote cysteine residue located outside of the canonical kinase domain, providing an unanticipated means of achieving selectivity for CDK7. Cancer cell-line profiling indicates that a subset of cancer cell lines, including human T-cell acute lymphoblastic leukaemia (T-ALL), have exceptional sensitivity to THZ1. Genome-wide analysis in Jurkat T-ALL cells shows that THZ1 disproportionally affects transcription of RUNX1 and suggests that sensitivity to THZ1 may be due to vulnerability conferred by the RUNX1 super-enhancer and the key role of RUNX1 in the core transcriptional regulatory circuitry of these tumour cells. Pharmacological modulation of CDK7 kinase activity may thus provide an approach to identify and treat tumour types that are dependent on transcription for maintenance of the oncogenic state., National Institutes of Health (U.S.) (Grant HG002668), National Institutes of Health (U.S.) (Grant CA109901)

Published
2015

42. Harnessing synthetic lethality to predict the response to cancer treatment.

Author

Joo Sang Lee, Das, Avinash, Jerby-Arnon, Livnat, Arafeh, Rand, Auslander, Noam, Davidson, Matthew, McGarry, Lynn, James, Daniel, Amzallag, Arnaud, Seung Gu Park, Kuoyuan Cheng, Robinson, Welles, Atias, Dikla, Stossel, Chani, Buzhor, Ella, Stein, Gidi, Waterfall, Joshua J., Meltzer, Paul S., Golan, Talia, and Hannenhalli, Sridhar

Subjects
CANCER treatment, DRUG efficacy, SYNTHETIC biology, ISLANDS
Abstract

While synthetic lethality (SL) holds promise in developing effective cancer therapies, SL candidates found via experimental screens often have limited translational value. Here we present a data-driven approach, ISLE (identification of clinically relevant synthetic lethality), that mines TCGA cohort to identify the most likely clinically relevant SL interactions (cSLi) from a given candidate set of lab-screened SLi. We first validate ISLE via a benchmark of large-scale drug response screens and by predicting drug efficacy in mouse xenograft models. We then experimentally test a select set of predicted cSLi via new screening experiments, validating their predicted context-specific sensitivity in hypoxic vs normoxic conditions and demonstrating cSLi’s utility in predicting synergistic drug combinations. We show that cSLi can successfully predict patients’ drug treatment response and provide patient stratification signatures. ISLE thus complements existing actionable mutation-based methods for precision cancer therapy, offering an opportunity to expand its scope to the whole genome. [ABSTRACT FROM AUTHOR]

Published
2018
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44. Landscape of Targeted Anti-Cancer Drug Synergies in Melanoma Identifies a Novel BRAF-VEGFR/PDGFR Combination Treatment

Author

Friedman, Adam A., primary, Amzallag, Arnaud, additional, Pruteanu-Malinici, Iulian, additional, Baniya, Subash, additional, Cooper, Zachary A., additional, Piris, Adriano, additional, Hargreaves, Leeza, additional, Igras, Vivien, additional, Frederick, Dennie T., additional, Lawrence, Donald P., additional, Haber, Daniel A., additional, Flaherty, Keith T., additional, Wargo, Jennifer A., additional, Ramaswamy, Sridhar, additional, Benes, Cyril H., additional, and Fisher, David E., additional

Published
2015
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45. Abstract 4690: Next-generation screen for integrative subtyping and target discovery for KRAS-mutant cancer

Author

Yuan, Tina L., primary, Bagni, Rachel, additional, Yi, Ming, additional, Amzallag, Arnaud, additional, Afghani, Shervin, additional, Beam, Katie, additional, Burgan, William, additional, Fer, Nicole, additional, Garvey, Leslie, additional, Smith, Brian, additional, Waters, Andrew, additional, Stephens, Robert, additional, Benes, Cyril, additional, and McCormick, Frank, additional

Published
2015
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48. Effects of base-pair sequence, nicks and gaps on DNA minicircle shapes:analysis and experiment

Author

Amzallag, Arnaud

Abstract

DNA is a long polymer with the form of a double helix of about two nanometers diameter (2.10-9 meters). It is composed of nucleotides whose sequence carries the information of heredity. The four possible nucleotides have slightly different geometries, and their sequence along the DNA molecule are thought to influence the shape and the stiffness of the double helix on a scale of few tens to a few hundred base pairs, and thereby its biological activity. DNA minicircles (or miniplasmids) are closed loops with lengths of the order of a few tens or hundreds of base pairs in which the double helix bends around to close on its own tail with some number of twists. Its minimal energy shape and its energy of formation depend on the sequence of base pairs, and can be efficiently computed by polymer and rod models, if shape and stiffness parameters of DNA are provided as inputs. This structure is therefore an interesting experimental motif to test sequence-dependent mechanical properties of the DNA molecule. The purpose of this thesis is to explore the experimental methods to determine the shape and free energy of formation of DNA minicircles. The shapes have been be determined from cryo-electron micrographs. Efficiency of formation has been investigated by a novel method called annealing-cyclization. Cryo-electron microscopy allows observation of very small molecules (here 17 or 11 nm diameter) in vitrified water, in order to keep the 3D shape of the molecules as close as possible to the shape they had in solution. In Chapter 1, I used stereo cryo-electron micrographs to determine and compare the three-dimensional shape of 95 individual DNA minicircles of 158 base pairs, which were identical in sequence except within a 18 bp block which contained either a TATA box sequence or a CAP site. I defined the notion of shape-distance which I used to estimate the error of reconstruction, and I detected clusters of shapes using an appropriate sorting algorithm. However the cluster did not seem to be associated with the variable sequence (TATA or CAP). I then analyzed (in Chapter 2) two-dimensional shapes of shorter DNA minicircles (94 bp) determined by negative staining electron microscopy, designed with either two nicks (breaks in one of the strands) or two gaps (missing nucleotides) at diametrically opposite sites of the minicircles. I observed that the gapped minicircles have an elongated shape with respect to the nicked minicircles, and I used this result together with the results of atomic level molecular dynamics simulations to conclude that the gap flexibility, perhaps together with base unpairing at the gap site, is responsible for this elongated minicircle shape. Finally, I proposed a ligase-free assay to measure the minicircle formation efficiency, which can give a high yield of nicked minicircles. The method avoids the use of ligase and the associated concerns about the effect of ligase concentration on the measurements. I determined an equation from a chemical model of the reaction that fits the experimental data, and I defined the Ja factor which gives a measure of the cyclization yield independent of DNA initial concentration. This method seems to confirm that minicircles with two gaps cyclize more efficiently that minicircles with two nicks, probably because of the gap flexibility. As a perspective, the conclusions of this thesis could be used for the design of minicircle constructs whose shape would be sensitive enough to sequence mutation in order to be detected by electron microscopy. Such shapes could be then compared, thanks to the shape-distance tool defined herein, to shapes computed with known or putative DNA models.

Published
2007
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49. Distinct, strict requirements for Gfi-1b in adult bone marrow red cell and platelet generation

Author

Foudi, Adlen, primary, Kramer, Daniel J., additional, Qin, Jinzhong, additional, Ye, Denise, additional, Behlich, Anna-Sophie, additional, Mordecai, Scott, additional, Preffer, Frederic I., additional, Amzallag, Arnaud, additional, Ramaswamy, Sridhar, additional, Hochedlinger, Konrad, additional, Orkin, Stuart H., additional, and Hock, Hanno, additional

Published
2014
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