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137 results on '"Aronchik, Ida"'

1. BET inhibitor trotabresib in heavily pretreated patients with solid tumors and diffuse large B-cell lymphomas

Author

Moreno, Victor, Vieito, Maria, Sepulveda, Juan Manuel, Galvao, Vladimir, Hernández-Guerrero, Tatiana, Doger, Bernard, Saavedra, Omar, Carlo-Stella, Carmelo, Michot, Jean-Marie, Italiano, Antoine, Magagnoli, Massimo, Carpio, Cecilia, Pinto, Antonio, Sarmiento, Rafael, Amoroso, Barbara, Aronchik, Ida, Filvaroff, Ellen, Hanna, Bishoy, Wei, Xin, Nikolova, Zariana, and Braña, Irene

Published
2023
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3. Supplementary Table S8 from Translational and Therapeutic Evaluation of RAS-GTP Inhibition by RMC-6236 in RAS-Driven Cancers

Author

Jiang, Jingjing, primary, Jiang, Lingyan, primary, Maldonato, Benjamin J., primary, Wang, Yingyun, primary, Holderfield, Matthew, primary, Aronchik, Ida, primary, Winters, Ian P., primary, Salman, Zeena, primary, Blaj, Cristina, primary, Menard, Marie, primary, Brodbeck, Jens, primary, Chen, Zhe, primary, Wei, Xing, primary, Rosen, Michael J., primary, Gindin, Yevgeniy, primary, Lee, Bianca J., primary, Evans, James W., primary, Chang, Stephanie, primary, Wang, Zhican, primary, Seamon, Kyle J., primary, Parsons, Dylan, primary, Cregg, James, primary, Marquez, Abby, primary, Tomlinson, Aidan C.A., primary, Yano, Jason K., primary, Knox, John E., primary, Quintana, Elsa, primary, Aguirre, Andrew J., primary, Arbour, Kathryn C., primary, Reed, Abby, primary, Gustafson, W. Clay, primary, Gill, Adrian L., primary, Koltun, Elena S., primary, Wildes, David, primary, Smith, Jacqueline A.M., primary, Wang, Zhengping, primary, and Singh, Mallika, primary

Published
2024
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4. Supplementary Figure S1-S6 from Translational and Therapeutic Evaluation of RAS-GTP Inhibition by RMC-6236 in RAS-Driven Cancers

Author

Jiang, Jingjing, primary, Jiang, Lingyan, primary, Maldonato, Benjamin J., primary, Wang, Yingyun, primary, Holderfield, Matthew, primary, Aronchik, Ida, primary, Winters, Ian P., primary, Salman, Zeena, primary, Blaj, Cristina, primary, Menard, Marie, primary, Brodbeck, Jens, primary, Chen, Zhe, primary, Wei, Xing, primary, Rosen, Michael J., primary, Gindin, Yevgeniy, primary, Lee, Bianca J., primary, Evans, James W., primary, Chang, Stephanie, primary, Wang, Zhican, primary, Seamon, Kyle J., primary, Parsons, Dylan, primary, Cregg, James, primary, Marquez, Abby, primary, Tomlinson, Aidan C.A., primary, Yano, Jason K., primary, Knox, John E., primary, Quintana, Elsa, primary, Aguirre, Andrew J., primary, Arbour, Kathryn C., primary, Reed, Abby, primary, Gustafson, W. Clay, primary, Gill, Adrian L., primary, Koltun, Elena S., primary, Wildes, David, primary, Smith, Jacqueline A.M., primary, Wang, Zhengping, primary, and Singh, Mallika, primary

Published
2024
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5. Supplementary Method from Translational and Therapeutic Evaluation of RAS-GTP Inhibition by RMC-6236 in RAS-Driven Cancers

Author

Jiang, Jingjing, primary, Jiang, Lingyan, primary, Maldonato, Benjamin J., primary, Wang, Yingyun, primary, Holderfield, Matthew, primary, Aronchik, Ida, primary, Winters, Ian P., primary, Salman, Zeena, primary, Blaj, Cristina, primary, Menard, Marie, primary, Brodbeck, Jens, primary, Chen, Zhe, primary, Wei, Xing, primary, Rosen, Michael J., primary, Gindin, Yevgeniy, primary, Lee, Bianca J., primary, Evans, James W., primary, Chang, Stephanie, primary, Wang, Zhican, primary, Seamon, Kyle J., primary, Parsons, Dylan, primary, Cregg, James, primary, Marquez, Abby, primary, Tomlinson, Aidan C.A., primary, Yano, Jason K., primary, Knox, John E., primary, Quintana, Elsa, primary, Aguirre, Andrew J., primary, Arbour, Kathryn C., primary, Reed, Abby, primary, Gustafson, W. Clay, primary, Gill, Adrian L., primary, Koltun, Elena S., primary, Wildes, David, primary, Smith, Jacqueline A.M., primary, Wang, Zhengping, primary, and Singh, Mallika, primary

Published
2024
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6. Data from Translational and Therapeutic Evaluation of RAS-GTP Inhibition by RMC-6236 in RAS-Driven Cancers

Author

Jiang, Jingjing, primary, Jiang, Lingyan, primary, Maldonato, Benjamin J., primary, Wang, Yingyun, primary, Holderfield, Matthew, primary, Aronchik, Ida, primary, Winters, Ian P., primary, Salman, Zeena, primary, Blaj, Cristina, primary, Menard, Marie, primary, Brodbeck, Jens, primary, Chen, Zhe, primary, Wei, Xing, primary, Rosen, Michael J., primary, Gindin, Yevgeniy, primary, Lee, Bianca J., primary, Evans, James W., primary, Chang, Stephanie, primary, Wang, Zhican, primary, Seamon, Kyle J., primary, Parsons, Dylan, primary, Cregg, James, primary, Marquez, Abby, primary, Tomlinson, Aidan C.A., primary, Yano, Jason K., primary, Knox, John E., primary, Quintana, Elsa, primary, Aguirre, Andrew J., primary, Arbour, Kathryn C., primary, Reed, Abby, primary, Gustafson, W. Clay, primary, Gill, Adrian L., primary, Koltun, Elena S., primary, Wildes, David, primary, Smith, Jacqueline A.M., primary, Wang, Zhengping, primary, and Singh, Mallika, primary

Published
2024
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7. Abstract B080: Mutant-selective KRASG12D(ON) inhibitor suppresses proliferation in vitro and tumor growth in vivo of KrasG12D GEMM-derived PDAC organoids

Author

Labrecque, Mark P., primary, Jiang, Lingyan, additional, Nasholm, Nicole, additional, Nayak, Biswadeep, additional, Yu, Xinxing, additional, Song, Avian, additional, Weller, Caroline, additional, Evans, James W., additional, Zafra, Maria Paz, additional, Parsons, Marie, additional, Menard, Marie, additional, Dow, Lukas E., additional, Jiang, Jingjing, additional, Aronchik, Ida, additional, and Singh, Mallika, additional

Published
2024
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8. Cooperative antiproliferative signaling by aspirin and indole-3-carbinol targets microphthalmia-associated transcription factor gene expression and promoter activity in human melanoma cells

Author

Poindexter, Kevin M, Matthew, Susanne, Aronchik, Ida, and Firestone, Gary L

Subjects
Biochemistry and Cell Biology, Biological Sciences, Human Genome, Genetics, Cancer, Aetiology, Development of treatments and therapeutic interventions, 5.1 Pharmaceuticals, 2.1 Biological and endogenous factors, Aspirin, Cell Cycle, Cell Line, Tumor, Cell Proliferation, Down-Regulation, Drug Synergism, Gene Expression, Humans, Indoles, Melanoma, Microphthalmia-Associated Transcription Factor, Promoter Regions, Genetic, Signal Transduction, Wnt Signaling Pathway, Indole-3-carbinol, LEF1, Melanoma cells, Microphthalmia-associated transcription factor, Wnt signaling, Toxicology, Biochemistry and cell biology
Abstract

Antiproliferative signaling of combinations of the nonsteroidal anti-inflammatory drug acetylsalicylic acid (aspirin) and indole-3-carbinol (I3C), a natural indolecarbinol compound derived from cruciferous vegetables, was investigated in human melanoma cells. Melanoma cell lines with distinct mutational profiles were sensitive to different extents to the antiproliferative response of aspirin, with oncogenic BRAF-expressing G361 cells and wild-type BRAF-expressing SK-MEL-30 cells being the most responsive. I3C triggered a strong proliferative arrest of G361 melanoma cells and caused only a modest decrease in the proliferation of SK-MEL-30 cells. In both cell lines, combinations of aspirin and I3C cooperatively arrested cell proliferation and induced a G1 cell cycle arrest, and nearly ablated protein and transcript levels of the melanocyte master regulator microphthalmia-associated transcription factor isoform M (MITF-M). In melanoma cells transfected with a -333/+120-bp MITF-M promoter-luciferase reporter plasmid, treatment with aspirin and I3C cooperatively disrupted MITF-M promoter activity, which accounted for the loss of MITF-M gene products. Mutational analysis revealed that the aspirin required the LEF1 binding site, whereas I3C required the BRN2 binding site to mediate their combined and individual effects on MITF-M promoter activity. Consistent with LEF1 being a downstream effector of Wnt signaling, aspirin, but not I3C, downregulated protein levels of the Wnt co-receptor LDL receptor-related protein-6 and β-catenin and upregulated the β-catenin destruction complex component Axin. Taken together, our results demonstrate that aspirin-regulated Wnt signaling and I3C-targeted signaling pathways converge at distinct DNA elements in the MITF-M promoter to cooperatively disrupt MITF-M expression and melanoma cell proliferation.

Published
2016

9. The Antiproliferative Response of Indole-3-Carbinol in Human Melanoma Cells Is Triggered by an Interaction with NEDD4-1 and Disruption of Wild-Type PTEN Degradation

Author

Aronchik, Ida, Kundu, Aishwarya, Quirit, Jeanne G, and Firestone, Gary L

Subjects
Biochemistry and Cell Biology, Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Biological Sciences, Complementary and Integrative Health, Cancer, Prevention, Aetiology, 2.1 Biological and endogenous factors, Animals, Apoptosis, Calorimetry, Cell Cycle, Cell Line, Tumor, Cell Proliferation, Computer Simulation, Down-Regulation, Endosomal Sorting Complexes Required for Transport, Humans, Indoles, Melanoma, Mice, Nude, Models, Molecular, Nedd4 Ubiquitin Protein Ligases, PTEN Phosphohydrolase, Proteasome Endopeptidase Complex, Protein Binding, Protein Stability, Protein Structure, Secondary, Proteolysis, Ubiquitin-Protein Ligases, Ubiquitination, Xenograft Model Antitumor Assays, Developmental Biology, Oncology & Carcinogenesis, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract

UnlabelledHuman melanoma cells displaying distinct PTEN genotypes were used to assess the cellular role of this important tumor-suppressor protein in the antiproliferative response induced by the chemopreventative agent indole-3-carbinol (I3C), a natural indolecarbinol compound derived from the breakdown of glucobrassicin produced in cruciferous vegetables such as broccoli and Brussels sprouts. I3C induced a G1-phase cell-cycle arrest and apoptosis by stabilization of PTEN in human melanoma cells that express wild-type PTEN, but not in cells with mutant or null PTEN genotypes. Importantly, normal human epidermal melanocytes were unaffected by I3C treatment. In wild-type PTEN-expressing melanoma xenografts, formed in athymic mice, I3C inhibited the in vivo tumor growth rate and increased PTEN protein levels in the residual tumors. Mechanistically, I3C disrupted the ubiquitination of PTEN by NEDD4-1 (NEDD4), which prevented the proteasome-mediated degradation of PTEN without altering its transcript levels. RNAi-mediated knockdown of PTEN prevented the I3C-induced apoptotic response, whereas knockdown of NEDD4-1 mimicked the I3C apoptotic response, stabilized PTEN protein levels, and downregulated phosphorylated AKT-1 levels. Co-knockdown of PTEN and NEDD4-1 revealed that I3C-regulated apoptotic signaling through NEDD4-1 requires the presence of the wild-type PTEN protein. Finally, in silico structural modeling, in combination with isothermal titration calorimetry analysis, demonstrated that I3C directly interacts with purified NEDD4-1 protein.ImplicationsThis study identifies NEDD4-1 as a new I3C target protein, and that the I3C disruption of NEDD4-1 ubiquitination activity triggers the stabilization of the wild-type PTEN tumor suppressor to induce an antiproliferative response in melanoma. Mol Cancer Res; 12(11); 1621-34. ©2014 AACR.

Published
2014

11. Neonatal development of the stratum corneum pH gradient: localization and mechanisms leading to emergence of optimal barrier function.

Author

Behne, Martin J, Barry, Nicholas P, Hanson, Kerry M, Aronchik, Ida, Clegg, Robert W, Gratton, Enrico, Feingold, Kenneth, Holleran, Walter M, Elias, Peter M, and Mauro, Theodora M

Subjects
Epidermis, Animals, Animals, Newborn, Rats, Rats, Sprague-Dawley, Acids, Hydrogen, Glucosylceramidase, Tissue Distribution, Aging, Parturition, Hydrogen-Ion Concentration, Lipid Metabolism, neonatal rat, stratum corneum pH, NHE1, FLIM, barrier function, Newborn, Sprague-Dawley, Dermatology & Venereal Diseases, Clinical Sciences, Oncology and Carcinogenesis
Abstract

Although basal permeability barrier function is established at birth, the higher risk for infections, dermatitis, and percutaneous absorption of toxic agents may indicate incomplete permeability barrier maturation in the early neonatal period. Since stratum corneum (SC) acidification in adults is required for normal permeability barrier homeostasis, and lipid processing occurs via acidic pH dependent enzymes, we hypothesized that, in parallel with the less acidic surface pH, newborn SC would exhibit signs of incomplete barrier formation. Fluorescence lifetime imaging reveals that neonatal rat SC acidification first becomes evident by postnatal day 3, in extracellular "microdomains" at the SC- stratum granulosum (SG) interface, where pH-sensitive lipid processing is known to occur. This localized acidification correlated temporally with efficient processing of secreted lamellar body contents to mature extracellular lamellar bilayers. Since expression of the key acidifying mechanism NHE1 is maximal just prior to birth, and gradually declines over the first postnatal week, suboptimal SC acidification at birth cannot be attributed to insufficient NHE1 expression, but could instead reflect reduced NHE1 activity. Expression of the key lipid processing enzyme, beta-glucocerebrosidase (beta-GlcCer'ase), develops similar to NHE1, excluding a lack of beta-GlcCer'ase protein as rate limiting for efficient lipid processing. These results define a postnatal development consisting of initial acidification in the lower SC followed by outward progression, which is accompanied by formation of mature extracellular lamellar membranes. Thus, full barrier competence appears to require the extension of acidification in microdomains from the SC/SG interface outward toward the skin surface in the immediate postnatal period.

Published
2003

12. Abstract 526: RMC-9805, a first-in-class, mutant-selective, covalent and oral KRASG12D(ON) inhibitor that induces apoptosis and drives tumor regression in preclinical models of KRASG12D cancers

Author

Jiang, Lingyan, primary, Menard, Marie, additional, Weller, Caroline, additional, Wang, Zhican, additional, Burnett, Les, additional, Aronchik, Ida, additional, Steele, Shelby, additional, Flagella, Mike, additional, Zhao, Ruiping, additional, Evans, James W W., additional, Chin, Shook, additional, Chou, Kang-Jye, additional, Mu, Yunming, additional, Longhi, Michael, additional, McDowell, Laura, additional, Knox, John E., additional, Gill, Adrian, additional, Smith, Jacqueline A., additional, Singh, Mallika, additional, Quintana, Elsa, additional, and Jiang, Jingjing, additional

Published
2023
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13. Supplementary Tables and Figures from Efficacy of a Covalent ERK1/2 Inhibitor, CC-90003, in KRAS-Mutant Cancer Models Reveals Novel Mechanisms of Response and Resistance

Author

Aronchik, Ida, primary, Dai, Yumin, primary, Labenski, Matt, primary, Barnes, Carmen, primary, Jones, Terri, primary, Qiao, Lixin, primary, Beebe, Lisa, primary, Malek, Mehnaz, primary, Elis, Winfried, primary, Shi, Tao, primary, Mavrommatis, Konstantinos, primary, Bray, Gordon L., primary, and Filvaroff, Ellen H., primary

Published
2023
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14. Supplementary figure legends and supplementary methods from Efficacy of a Covalent ERK1/2 Inhibitor, CC-90003, in KRAS-Mutant Cancer Models Reveals Novel Mechanisms of Response and Resistance

Author

Aronchik, Ida, primary, Dai, Yumin, primary, Labenski, Matt, primary, Barnes, Carmen, primary, Jones, Terri, primary, Qiao, Lixin, primary, Beebe, Lisa, primary, Malek, Mehnaz, primary, Elis, Winfried, primary, Shi, Tao, primary, Mavrommatis, Konstantinos, primary, Bray, Gordon L., primary, and Filvaroff, Ellen H., primary

Published
2023
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15. Supplementary Figures 1 - 4 from Novel Potent and Selective Inhibitors of p90 Ribosomal S6 Kinase Reveal the Heterogeneity of RSK Function in MAPK-Driven Cancers

Author

Aronchik, Ida, primary, Appleton, Brent A., primary, Basham, Stephen E., primary, Crawford, Kenneth, primary, Del Rosario, Mercedita, primary, Doyle, Laura V., primary, Estacio, William F., primary, Lan, Jiong, primary, Lindvall, Mika K., primary, Luu, Catherine A., primary, Ornelas, Elizabeth, primary, Venetsanakos, Eleni, primary, Shafer, Cynthia M., primary, and Jefferson, Anne B., primary

Published
2023
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16. Data from Efficacy of a Covalent ERK1/2 Inhibitor, CC-90003, in KRAS-Mutant Cancer Models Reveals Novel Mechanisms of Response and Resistance

Author

Aronchik, Ida, primary, Dai, Yumin, primary, Labenski, Matt, primary, Barnes, Carmen, primary, Jones, Terri, primary, Qiao, Lixin, primary, Beebe, Lisa, primary, Malek, Mehnaz, primary, Elis, Winfried, primary, Shi, Tao, primary, Mavrommatis, Konstantinos, primary, Bray, Gordon L., primary, and Filvaroff, Ellen H., primary

Published
2023
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17. Supplementary Methods from Novel Potent and Selective Inhibitors of p90 Ribosomal S6 Kinase Reveal the Heterogeneity of RSK Function in MAPK-Driven Cancers

Author

Aronchik, Ida, primary, Appleton, Brent A., primary, Basham, Stephen E., primary, Crawford, Kenneth, primary, Del Rosario, Mercedita, primary, Doyle, Laura V., primary, Estacio, William F., primary, Lan, Jiong, primary, Lindvall, Mika K., primary, Luu, Catherine A., primary, Ornelas, Elizabeth, primary, Venetsanakos, Eleni, primary, Shafer, Cynthia M., primary, and Jefferson, Anne B., primary

Published
2023
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18. Supplementary Table 2 from Novel Potent and Selective Inhibitors of p90 Ribosomal S6 Kinase Reveal the Heterogeneity of RSK Function in MAPK-Driven Cancers

Author

Aronchik, Ida, primary, Appleton, Brent A., primary, Basham, Stephen E., primary, Crawford, Kenneth, primary, Del Rosario, Mercedita, primary, Doyle, Laura V., primary, Estacio, William F., primary, Lan, Jiong, primary, Lindvall, Mika K., primary, Luu, Catherine A., primary, Ornelas, Elizabeth, primary, Venetsanakos, Eleni, primary, Shafer, Cynthia M., primary, and Jefferson, Anne B., primary

Published
2023
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19. Supplementary Table 1 from Novel Potent and Selective Inhibitors of p90 Ribosomal S6 Kinase Reveal the Heterogeneity of RSK Function in MAPK-Driven Cancers

Author

Aronchik, Ida, primary, Appleton, Brent A., primary, Basham, Stephen E., primary, Crawford, Kenneth, primary, Del Rosario, Mercedita, primary, Doyle, Laura V., primary, Estacio, William F., primary, Lan, Jiong, primary, Lindvall, Mika K., primary, Luu, Catherine A., primary, Ornelas, Elizabeth, primary, Venetsanakos, Eleni, primary, Shafer, Cynthia M., primary, and Jefferson, Anne B., primary

Published
2023
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20. Supplementary Figure Legends from Novel Potent and Selective Inhibitors of p90 Ribosomal S6 Kinase Reveal the Heterogeneity of RSK Function in MAPK-Driven Cancers

Author

Aronchik, Ida, primary, Appleton, Brent A., primary, Basham, Stephen E., primary, Crawford, Kenneth, primary, Del Rosario, Mercedita, primary, Doyle, Laura V., primary, Estacio, William F., primary, Lan, Jiong, primary, Lindvall, Mika K., primary, Luu, Catherine A., primary, Ornelas, Elizabeth, primary, Venetsanakos, Eleni, primary, Shafer, Cynthia M., primary, and Jefferson, Anne B., primary

Published
2023
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21. Supplementary Data from Phase I Study of Lysine-Specific Demethylase 1 Inhibitor, CC-90011, in Patients with Advanced Solid Tumors and Relapsed/Refractory Non-Hodgkin Lymphoma

Author

Hollebecque, Antoine, primary, Salvagni, Stefania, primary, Plummer, Ruth, primary, Isambert, Nicolas, primary, Niccoli, Patricia, primary, Capdevila, Jaume, primary, Curigliano, Giuseppe, primary, Moreno, Victor, primary, Martin-Romano, Patricia, primary, Baudin, Eric, primary, Arias, Marina, primary, Mora, Sheila, primary, de Alvaro, Juan, primary, Di Martino, Jorge, primary, Parra-Palau, Josep L., primary, Sánchez-Pérez, Tania, primary, Aronchik, Ida, primary, Filvaroff, Ellen H., primary, Lamba, Manisha, primary, Nikolova, Zariana, primary, and de Bono, Johann S., primary

Published
2023
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22. Supplementary Figure S1 from Phase I Study of Lysine-Specific Demethylase 1 Inhibitor, CC-90011, in Patients with Advanced Solid Tumors and Relapsed/Refractory Non-Hodgkin Lymphoma

Author

Hollebecque, Antoine, primary, Salvagni, Stefania, primary, Plummer, Ruth, primary, Isambert, Nicolas, primary, Niccoli, Patricia, primary, Capdevila, Jaume, primary, Curigliano, Giuseppe, primary, Moreno, Victor, primary, Martin-Romano, Patricia, primary, Baudin, Eric, primary, Arias, Marina, primary, Mora, Sheila, primary, de Alvaro, Juan, primary, Di Martino, Jorge, primary, Parra-Palau, Josep L., primary, Sánchez-Pérez, Tania, primary, Aronchik, Ida, primary, Filvaroff, Ellen H., primary, Lamba, Manisha, primary, Nikolova, Zariana, primary, and de Bono, Johann S., primary

Published
2023
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25. Trotabresib, an oral potent bromodomain and extraterminal inhibitor, in patients with high-grade gliomas: A phase I, “window-of-opportunity” study

Author

Moreno, Victor, primary, Manuel Sepúlveda, Juan, additional, Reardon, David A, additional, Pérez-Núñez, Ángel, additional, González León, Pedro, additional, Hanna, Bishoy, additional, Filvaroff, Ellen, additional, Aronchik, Ida, additional, Chang, Henry, additional, Amoroso, Barbara, additional, Zuraek, Marlene, additional, Sanchez-Perez, Tania, additional, Mendez, Cristina, additional, Stephens, Daniel, additional, Nikolova, Zariana, additional, and Vogelbaum, Michael A, additional

Published
2022
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26. Trotabresib (CC-90010) in combination with adjuvant temozolomide or concomitant temozolomide plus radiotherapy in patients with newly diagnosed glioblastoma

Author

Vieito, Maria, Simonelli, Matteo, De Vos, Filip, Moreno, Victor, Geurts, Marjolein, Lorenzi, Elena, Macchini, Marina, Van Den Bent, Martin J., Del Conte, Gianluca, De Jonge, Maja, Martín-Soberón, Maria Cruz, Amoroso, Barbara, Sanchez-Perez, Tania, Zuraek, Marlene, Hanna, Bishoy, Aronchik, Ida, Filvaroff, Ellen, Chang, Henry, Mendez, Cristina, Arias Parro, Marina, Wei, Xin, Nikolova, Zariana, Sepulveda, Juan Manuel, Vieito, Maria, Simonelli, Matteo, De Vos, Filip, Moreno, Victor, Geurts, Marjolein, Lorenzi, Elena, Macchini, Marina, Van Den Bent, Martin J., Del Conte, Gianluca, De Jonge, Maja, Martín-Soberón, Maria Cruz, Amoroso, Barbara, Sanchez-Perez, Tania, Zuraek, Marlene, Hanna, Bishoy, Aronchik, Ida, Filvaroff, Ellen, Chang, Henry, Mendez, Cristina, Arias Parro, Marina, Wei, Xin, Nikolova, Zariana, and Sepulveda, Juan Manuel

Abstract

Background: Standard-of-care treatment for newly diagnosed glioblastoma (ndGBM), consisting of surgery followed by radiotherapy (RT) and temozolomide (TMZ), has improved outcomes compared with RT alone; however, prognosis remains poor. Trotabresib, a novel bromodomain and extraterminal inhibitor, has demonstrated antitumor activity in patients with high-grade gliomas. Methods: In this phase Ib, dose-escalation study (NCT04324840), we investigated trotabresib 15, 30, and 45 mg combined with TMZ in the adjuvant setting and trotabresib 15 and 30 mg combined with TMZ+RT in the concomitant setting in patients with ndGBM. Primary endpoints were to determine safety, tolerability, maximum tolerated dose, and/or recommended phase II dose (RP2D) of trotabresib. Secondary endpoints were assessment of preliminary efficacy and pharmacokinetics. Pharmacodynamics were investigated as an exploratory endpoint. Results: The adjuvant and concomitant cohorts enrolled 18 and 14 patients, respectively. Trotabresib in combination with TMZ or TMZ+RT was well tolerated; most treatment-related adverse events were mild or moderate. Trotabresib pharmacokinetics and pharmacodynamics in both settings were consistent with previous data for trotabresib monotherapy. The RP2D of trotabresib was selected as 30 mg 4 days on/24 days off in both settings. At last follow-up, 5 (28%) and 6 (43%) patients remain on treatment in the adjuvant and concomitant settings, respectively, with 1 patient in the adjuvant cohort achieving complete response. Conclusions: Trotabresib combined with TMZ in the adjuvant setting and with TMZ+RT in the concomitant setting was safe and well tolerated in patients with ndGBM, with encouraging treatment durations. Trotabresib 30 mg was established as the RP2D in both settings.

Published
2022

27. Trotabresib (CC-90010) in combination with adjuvant temozolomide or concomitant temozolomide plus radiotherapy in patients with newly diagnosed glioblastoma

Author

MS Medische Oncologie, Cancer, Vieito, Maria, Simonelli, Matteo, de Vos, Filip, Moreno, Victor, Geurts, Marjolein, Lorenzi, Elena, Macchini, Marina, van den Bent, Martin J, Del Conte, Gianluca, de Jonge, Maja, Martín-Soberón, Maria Cruz, Amoroso, Barbara, Sanchez-Perez, Tania, Zuraek, Marlene, Hanna, Bishoy, Aronchik, Ida, Filvaroff, Ellen, Chang, Henry, Mendez, Cristina, Arias Parro, Marina, Wei, Xin, Nikolova, Zariana, Sepulveda, Juan Manuel, MS Medische Oncologie, Cancer, Vieito, Maria, Simonelli, Matteo, de Vos, Filip, Moreno, Victor, Geurts, Marjolein, Lorenzi, Elena, Macchini, Marina, van den Bent, Martin J, Del Conte, Gianluca, de Jonge, Maja, Martín-Soberón, Maria Cruz, Amoroso, Barbara, Sanchez-Perez, Tania, Zuraek, Marlene, Hanna, Bishoy, Aronchik, Ida, Filvaroff, Ellen, Chang, Henry, Mendez, Cristina, Arias Parro, Marina, Wei, Xin, Nikolova, Zariana, and Sepulveda, Juan Manuel

Published
2022

28. Trotabresib, an oral potent bromodomain and extraterminal inhibitor, in patients with high-grade gliomas: A phase I, "window-of-opportunity" study.

Author

Moreno, Victor, Sepúlveda, Juan Manuel, Reardon, David A, Pérez-Núñez, Ángel, León, Pedro González, Hanna, Bishoy, Filvaroff, Ellen, Aronchik, Ida, Chang, Henry, Amoroso, Barbara, Zuraek, Marlene, Sanchez-Perez, Tania, Mendez, Cristina, Stephens, Daniel, Nikolova, Zariana, and Vogelbaum, Michael A

Published
2023
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29. Clinical activity of CC‐90011, an oral, potent, and reversible LSD1 inhibitor, in advanced malignancies

Author

Hollebecque, Antoine, primary, Salvagni, Stefania, additional, Plummer, Ruth, additional, Niccoli, Patricia, additional, Capdevila, Jaume, additional, Curigliano, Giuseppe, additional, Moreno, Victor, additional, de Braud, Filippo, additional, de Villambrosia, Sonia Gonzalez, additional, Martin‐Romano, Patricia, additional, Baudin, Eric, additional, Arias, Marina, additional, de Alvaro, Juan, additional, Parra‐Palau, Josep L., additional, Sánchez‐Pérez, Tania, additional, Aronchik, Ida, additional, Filvaroff, Ellen H., additional, Lamba, Manisha, additional, Nikolova, Zariana, additional, and de Bono, Johann S., additional

Published
2022
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31. Trotabresib (CC-90010) in combination with adjuvant temozolomide or concomitant temozolomide plus radiotherapy in patients with newly diagnosed glioblastoma

Author

Vieito, Maria, primary, Simonelli, Matteo, additional, de Vos, Filip, additional, Moreno, Victor, additional, Geurts, Marjolein, additional, Lorenzi, Elena, additional, Macchini, Marina, additional, van den Bent, Martin J, additional, Del Conte, Gianluca, additional, de Jonge, Maja, additional, Martín-Soberón, Maria Cruz, additional, Amoroso, Barbara, additional, Sanchez-Perez, Tania, additional, Zuraek, Marlene, additional, Hanna, Bishoy, additional, Aronchik, Ida, additional, Filvaroff, Ellen, additional, Chang, Henry, additional, Mendez, Cristina, additional, Arias Parro, Marina, additional, Wei, Xin, additional, Nikolova, Zariana, additional, and Sepulveda, Juan Manuel, additional

Published
2022
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32. CTNI-16. TROTABRESIB (CC-90010, BMS-986378), A REVERSIBLE, POTENT ORAL BROMODOMAIN AND EXTRATERMINAL INHIBITOR (BETi) IN PATIENTS WITH HIGH-GRADE GLIOMAS: A PHASE 1 OPEN-LABEL ‘WINDOW OF OPPORTUNITY’ STUDY

Author

Vogelbaum, Michael, primary, Sepulveda, Juan Manuel, additional, Reardon, David, additional, Hanna, Bishoy, additional, Filvaroff, Ellen, additional, Aronchik, Ida, additional, Amoroso, Barbara, additional, Zuraek, Marlene, additional, Sanchez-Perez, Tania, additional, Mendez, Cristina, additional, Nikolova, Zariana, additional, and Moreno, Victor, additional

Published
2021
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33. CTNI-51. ADJUVANT TROTABRESIB, A REVERSIBLE POTENT BROMODOMAIN AND EXTRATERMINAL INHIBITOR, PLUS TEMOZOLOMIDE IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA: INTERIM RESULTS FROM A PHASE 1B DOSE-FINDING STUDY

Author

Vieito, Maria, primary, Simonelli, Matteo, additional, de Vos, Filip, additional, Moreno, Victor, additional, Geurts, Marjolein, additional, Lorenzi, Elena, additional, Macchini, Marina, additional, van den Bent, Martin, additional, Del Conte, Gianluca, additional, de Jonge, Maja, additional, Amoroso, Barbara, additional, Sanchez-Perez, Tania, additional, Zuraek, Marlene, additional, Hanna, Bishoy, additional, Aronchik, Ida, additional, Filvaroff, Ellen, additional, Mendez, Cristina, additional, Wei, Xin, additional, Nikolova, Zariana, additional, and Sepulveda, Juan Manuel, additional

Published
2021
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34. Phase I Study of Lysine-Specific Demethylase 1 Inhibitor, CC-90011, in Patients with Advanced Solid Tumors and Relapsed/Refractory Non-Hodgkin Lymphoma

Author

Hollebecque, Antoine, primary, Salvagni, Stefania, additional, Plummer, Ruth, additional, Isambert, Nicolas, additional, Niccoli, Patricia, additional, Capdevila, Jaume, additional, Curigliano, Giuseppe, additional, Moreno, Victor, additional, Martin-Romano, Patricia, additional, Baudin, Eric, additional, Arias, Marina, additional, Mora, Sheila, additional, de Alvaro, Juan, additional, Di Martino, Jorge, additional, Parra-Palau, Josep L., additional, Sánchez-Pérez, Tania, additional, Aronchik, Ida, additional, Filvaroff, Ellen H., additional, Lamba, Manisha, additional, Nikolova, Zariana, additional, and de Bono, Johann S., additional

Published
2021
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40. Phase I study of CC-90010 in patients with advanced solid tumors and relapsed/refractory non-Hodgkin lymphoma (R/R NHL).

Author

Moreno, Victor, primary, Braña, Irene, additional, Sepulveda Sanchez, Juan Manuel Manuel, additional, Villar, Maria Vieito, additional, Hernandez-Guerrero, Tatiana, additional, Doger, Bernard, additional, Saavedra, Omar, additional, Ferrero, Olga, additional, Sarmiento, Rafael, additional, Arias, Marina, additional, De Alvaro, Juan, additional, DiMartino, Jorge F., additional, Zuraek, Marlene, additional, Sánchez Pérez, Tania, additional, Filvaroff, Ellen, additional, Aronchik, Ida, additional, Lamba, Manisha, additional, Hanna, Bishoy, additional, and Nikolova, Zariana G., additional

Published
2019
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41. Efficacy of a Covalent ERK1/2 Inhibitor, CC-90003, in KRAS-Mutant Cancer Models Reveals Novel Mechanisms of Response and Resistance

Author

Aronchik, Ida, primary, Dai, Yumin, additional, Labenski, Matt, additional, Barnes, Carmen, additional, Jones, Terri, additional, Qiao, Lixin, additional, Beebe, Lisa, additional, Malek, Mehnaz, additional, Elis, Winfried, additional, Shi, Tao, additional, Mavrommatis, Konstantinos, additional, Bray, Gordon L., additional, and Filvaroff, Ellen H., additional

Published
2019
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42. A phase Ia study of CC-90003, a selective extracellular signal-regulated kinase (ERK) inhibitor, in patients with relapsed or refractory BRAF or RAS-mutant tumors.

Author

Mita, Monica M., primary, LoRusso, Patricia, additional, McArthur, Grant A., additional, Kim, Edward S., additional, Bray, Gordon L., additional, Hock, Nanette H, additional, Laille, Eric J., additional, Aronchik, Ida, additional, Filvaroff, Ellen, additional, Wu, Xiaoling, additional, and Bendell, Johanna C., additional

Published
2017
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43. 2-Amino-7-substituted benzoxazole analogs as potent RSK2 inhibitors

Author

Costales, Abran, Mathur, Michelle, Ramurthy, Savithri, Lan, Jiong, Subramanian, Sharadha, Jain, Rama, Atallah, Gordana, Setti, Lina, Lindvall, Mika, Appleton, Brent A., Ornelas, Elizabeth, Feucht, Paul, Warne, Bob, Doyle, Laura, Basham, Stephen E., Aronchik, Ida, Jefferson, Anne B., and Shafer, Cynthia M.

Published
2014
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44. Novel Potent and Selective Inhibitors of p90 Ribosomal S6 Kinase Reveal the Heterogeneity of RSK Function in MAPK-Driven Cancers

Author

Aronchik, Ida, primary, Appleton, Brent A., additional, Basham, Stephen E., additional, Crawford, Kenneth, additional, Del Rosario, Mercedita, additional, Doyle, Laura V., additional, Estacio, William F., additional, Lan, Jiong, additional, Lindvall, Mika K., additional, Luu, Catherine A., additional, Ornelas, Elizabeth, additional, Venetsanakos, Eleni, additional, Shafer, Cynthia M., additional, and Jefferson, Anne B., additional

Published
2014
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50. The dietary phytochemical indole3-carbinol is a natural elastase enzymatic inhibitor that disrupts cyclin E protein processing.

Author

Nguyen, Hanh H., Aronchik, Ida, Brar, Gloria A., Nguyen, David H. H., Bjeldanes, Leonard F., and Firestone, Gary L.

Subjects
BRASSICA, CANCER cell proliferation, CYCLINS, ENZYME kinetics, ELASTASES, INDOLE, MOLECULAR phytochemicals, GENETICS of breast cancer
Abstract

lndole-3-carbinol (l3C), a naturally occurring component of Brassica vegetables, such as broccoli, cabbage, and Brussels sprouts, induces a G[sub1] cell-cycle arrest of human breast cancer cells, although the direct cellular targets that mediate this process are unknown. Treatment of highly invasive MDA-MB-231 breast cancer cells with I3C shifted the stable accumulation of cyclin E protein from the hyperactive lower-molecular-mass 35-kDa form that is associated with cancer cell proliferation and poor clinical outcomes to the 50-kDa cyclin E form that typically is expressed in normal mammary tissue. An in vitro cyclin E processing assay, in combination with zymography, demonstrated that 13C, but not its natural dimer, 3,3'-diindolylmethane, disrupts proteolytic processing of the 50-kDa cyclin E into the lower-molecular-mass forms by direct inhibition of human neutrophil elastase enzymatic activity. Analysis of elastase enzyme kinetics using either cyclin F or N-methoxysuccinyl-Ala-Ala-pro-val-p-nitroanalide as substrates demonstrated that 13C acts as a noncompetitive inhibitor of elastase activity with an inhibitory constant of ≈12 ~tM. Finally, siRNA ablation of neutrophil elastase protein production in MDAMB-231 cells mimicked the 13C-disrupted processing of the 50-kDa cyclin E protein and the indole-induced cell-cycle arrest. Taken together, our results demonstrate that elastase is the first identified specific target protein for 13C and that the direct 13C inhibition of elastase enzymatic activity implicates the potential use of this indole, or related compounds, in targeted therapies of human breast cancers where high elastase levels are correlated with poor prognosis. [ABSTRACT FROM AUTHOR]

Published
2008
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