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Your search keyword '"Vito W. Rebecca"' showing total 6 results
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6 results on '"Vito W. Rebecca"'

1. Persister state-directed transitioning and vulnerability in melanoma

Author

Heike Chauvistré, Batool Shannan, Sheena M. Daignault-Mill, Robert J. Ju, Daniel Picard, Stefanie Egetemaier, Renáta Váraljai, Christine S. Gibhardt, Antonio Sechi, Farnusch Kaschani, Oliver Keminer, Samantha J. Stehbens, Qin Liu, Xiangfan Yin, Kirujan Jeyakumar, Felix C. E. Vogel, Clemens Krepler, Vito W. Rebecca, Linda Kubat, Smiths S. Lueong, Jan Forster, Susanne Horn, Marc Remke, Michael Ehrmann, Annette Paschen, Jürgen C. Becker, Iris Helfrich, Daniel Rauh, Markus Kaiser, Sheraz Gul, Meenhard Herlyn, Ivan Bogeski, José Neptuno Rodríguez-López, Nikolas K. Haass, Dirk Schadendorf, and Alexander Roesch

Subjects
Science
Abstract

Slow-cycling melanoma persister cells are characterised by a high, reversible expression of H3K4 demethylase KDM5B. Here, the authors use genetic and chemical methods to enforce a permanent high expression of KDM5B and show that these cells transit to a melanocytic differentiated state and undergo cell cycle arrest.

Published
2022
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2. Targeting SOX10-deficient cells to reduce the dormant-invasive phenotype state in melanoma

Author

Claudia Capparelli, Timothy J. Purwin, McKenna Glasheen, Signe Caksa, Manoela Tiago, Nicole Wilski, Danielle Pomante, Sheera Rosenbaum, Mai Q. Nguyen, Weijia Cai, Janusz Franco-Barraza, Richard Zheng, Gaurav Kumar, Inna Chervoneva, Ayako Shimada, Vito W. Rebecca, Adam E. Snook, Kim Hookim, Xiaowei Xu, Edna Cukierman, Meenhard Herlyn, and Andrew E. Aplin

Subjects
Science
Abstract

Mechanisms underlying tumor cell plasticity remain poorly understood. Here, the authors show the presence of a dormant-invasive SOX10- subpopulation in cutaneous melanoma that can be targeted by cIAP1/2 inhibitors.

Published
2022
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3. Tumor-infiltrating mast cells are associated with resistance to anti-PD-1 therapy

Author

Rajasekharan Somasundaram, Thomas Connelly, Robin Choi, Hyeree Choi, Anastasia Samarkina, Ling Li, Elizabeth Gregorio, Yeqing Chen, Rohit Thakur, Mohamed Abdel-Mohsen, Marilda Beqiri, Meaghan Kiernan, Michela Perego, Fang Wang, Min Xiao, Patricia Brafford, Xue Yang, Xiaowei Xu, Anthony Secreto, Gwenn Danet-Desnoyers, Daniel Traum, Klaus H. Kaestner, Alexander C. Huang, Denitsa Hristova, Joshua Wang, Mizuho Fukunaga-Kalabis, Clemens Krepler, Fang Ping-Chen, Xiangyang Zhou, Alexis Gutierrez, Vito W. Rebecca, Prashanthi Vonteddu, Farokh Dotiwala, Shashi Bala, Sonali Majumdar, Harsh Dweep, Jayamanna Wickramasinghe, Andrew V. Kossenkov, Jorge Reyes-Arbujas, Kenisha Santiago, Tran Nguyen, Johannes Griss, Frederick Keeney, James Hayden, Brian J. Gavin, David Weiner, Luis J. Montaner, Qin Liu, Lukas Peiffer, Jürgen Becker, Elizabeth M. Burton, Michael A. Davies, Michael T. Tetzlaff, Kar Muthumani, Jennifer A. Wargo, Dmitry Gabrilovich, and Meenhard Herlyn

Subjects
Science
Abstract

Immune checkpoint therapies (ICT) are promising for treating various cancers, but response rates vary. Here the authors show, in mouse models, that tumor-infiltrating mast cells colocalize with regulatory T cells, coincide with local reduction of MHC-I and CD8 T cells, and is associated with resistance to ICT, which can be reversed by c-kit inhibitor treatment.

Published
2021
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4. Pre-clinical modeling of cutaneous melanoma

Author

Vito W. Rebecca, Rajasekharan Somasundaram, and Meenhard Herlyn

Subjects
Science
Abstract

Despite the new targeted and immunotherapies for metastatic melanoma, several patients show therapeutic plateau. Here, the authors review the current pre-clinical models of cutaneous melanoma and discuss their strengths and limitations that may help with overcoming therapeutic plateau.

Published
2020
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5. Comprehensive characterization of 536 patient-derived xenograft models prioritizes candidatesfor targeted treatment

Author

Li Chen, Jacqueline Mudd, Michael Ittmann, Carol J. Bult, Amanda R. Kirane, Jelena Randjelovic, Stephen Scott, Yige Wu, Li Ding, Vashisht G. Yennu-Nanda, Jing Wang, Christopher D. Lanier, Maihi Fujita, Emilio Cortes-Sanchez, Sienna Rocha, Susan G. Hilsenbeck, Kian-Huat Lim, Fernanda Martins Rodrigues, Jill Rubinstein, Nicholas Mitsiades, Haiyin Lin, Jayamanna Wickramasinghe, Andrew Butterfield, Bryan E. Welm, Alana L. Welm, Jose P. Zevallos, Jason Held, Nicole B. Coggins, Song Cao, Yuanxin Xi, Brenda C. Timmons, Paul Lott, David Menter, Shunqiang Li, Tina Primeau, Fei Yang, Andrea Wang-Gillam, Ramaswamy Govindan, Dali Li, Brandi Davis-Dusenbery, Sara Seepo, Michael C. Wendl, Jeffrey Grover, Brian S. White, Clifford G. Tepper, Peter N. Robinson, Michael A. Davies, Zhengtao Chu, Michael W. Lloyd, Hua Sun, Xiaoshan Zhang, Tamara Stankovic, Dylan Fingerman, Anuj Srivastava, Luis G. Carvajal-Carmona, Don L. Gibbons, Lijun Yao, Rebecca Aft, Hongyong Zhang, Ismail Meraz, John DiGiovanna, Scott Kopetz, Ling Zhao, Guadalupe Polanco-Echeverry, Feng Chen, Jeremy Hoog, Matthew A. Wyczalkowski, George Xu, John D. Minna, Yi Xu, Julie Belmar, Xiaowei Xu, Luc Girard, Dennis A. Dean, Tijana Borovski, Chong-xian Pan, Cynthia X. Ma, Alexa Morales Arana, Yize Li, Turcin Saridogan, Steven B. Neuhauser, Sandra Scherer, Vicki Chin, Rose Tipton, David R. Gandara, Sherri R. Davies, Argun Akcakanat, Rajesh Patidar, Julie K. Schwarz, Soner Koc, Gao Boning, Michael Kim, Bryce P. Kirby, Yvonne A. Evrard, Hyunsil Park, Christian Frech, Chia-Kuei Mo, Ran Zhang, Brian A. Van Tine, Jonathan W. Reiss, Min Xiao, Xing Yi Woo, Tiffany Le, Ana Estrada, Xiaofeng Zheng, Jeffrey A. Moscow, Mourad Majidi, Nadezhda V. Terekhanova, Katherine Fuh, Erkan Yuca, Timothy A. Yap, Jianhua Zhang, Matthew J. Ellis, Shannon Westin, James H. Doroshow, Vito W. Rebecca, Moon S. Chen, Coya Tapia, Reyka G Jayasinghe, Jack A. Roth, Jithesh Augustine, Ryan C. Fields, Michae T. Tetzlaff, Michael T. Lewis, Kurt W. Evans, Ralph W. deVere White, Brian J. Sanderson, May Cho, Jeffrey H. Chuang, Tiffany Wallace, Ryan Jeon, Ted Toal, Matthew H. Bailey, Bert W. O'Malley, Katherine L. Nathanson, Qin Liu, Benjamin J. Raphael, Jingqin Luo, Salma Kaochar, Huiqin Chen, Rajasekharan Somasundaram, Daniel Cui Zhou, John F. DiPersio, Andrew V. Kossenkov, Bingliang Fang, Vanessa Jensen, Simone Zaccaria, Alexey Sorokin, Ai-Hong Ma, Sidharth V. Puram, Min Jin Ha, Meenhard Herlyn, R. Jay Mashl, Kelly Gale, Bingbing Dai, Lacey E. Dobrolecki, Chieh-Hsiang Yang, and Funda Meric-Bernstam

Subjects
endocrine system, Science, Druggability, General Physics and Astronomy, Genomics, Computational biology, Biology, Genome, digestive system, General Biochemistry, Genetics and Molecular Biology, Article, Research community, Multiple time, medicine, Cancer genomics, Cancer models, Tumor xenograft, Multidisciplinary, Cancer, General Chemistry, medicine.disease, Pharmacogenomics, Data integration, hormones, hormone substitutes, and hormone antagonists
Abstract

Development of candidate cancer treatments is a resource-intensive process, with the research community continuing to investigate options beyond static genomic characterization. Toward this goal, we have established the genomic landscapes of 536 patient-derived xenograft (PDX) models across 25 cancer types, together with mutation, copy number, fusion, transcriptomic profiles, and NCI-MATCH arms. Compared with human tumors, PDXs typically have higher purity and fit to investigate dynamic driver events and molecular properties via multiple time points from same case PDXs. Here, we report on dynamic genomic landscapes and pharmacogenomic associations, including associations between activating oncogenic events and drugs, correlations between whole-genome duplications and subclone events, and the potential PDX models for NCI-MATCH trials. Lastly, we provide a web portal having comprehensive pan-cancer PDX genomic profiles and source code to facilitate identification of more druggable events and further insights into PDXs’ recapitulation of human tumors., Patient-derived xenograft models (PDX) have been extensively used to study the molecular and clinical features of cancers. Here the authors present a cohort of 536 PDX models from 25 cancers, as well as their genomic and evolutionary profiles and their suitability for clinical trials.

Published
2021

6. Targeting SOX10-deficient cells to reduce the dormant-invasive phenotype state in melanoma

Author

Claudia, Capparelli, Timothy J, Purwin, McKenna, Glasheen, Signe, Caksa, Manoela, Tiago, Nicole, Wilski, Danielle, Pomante, Sheera, Rosenbaum, Mai Q, Nguyen, Weijia, Cai, Janusz, Franco-Barraza, Richard, Zheng, Gaurav, Kumar, Inna, Chervoneva, Ayako, Shimada, Vito W, Rebecca, Adam E, Snook, Kim, Hookim, Xiaowei, Xu, Edna, Cukierman, Meenhard, Herlyn, and Andrew E, Aplin

Subjects
Proto-Oncogene Proteins B-raf, Phenotype, Skin Neoplasms, SOXE Transcription Factors, Cell Line, Tumor, Tumor Microenvironment, Humans, Melanoma
Abstract

Cellular plasticity contributes to intra-tumoral heterogeneity and phenotype switching, which enable adaptation to metastatic microenvironments and resistance to therapies. Mechanisms underlying tumor cell plasticity remain poorly understood. SOX10, a neural crest lineage transcription factor, is heterogeneously expressed in melanomas. Loss of SOX10 reduces proliferation, leads to invasive properties, including the expression of mesenchymal genes and extracellular matrix, and promotes tolerance to BRAF and/or MEK inhibitors. We identify the class of cellular inhibitor of apoptosis protein-1/2 (cIAP1/2) inhibitors as inducing cell death selectively in SOX10-deficient cells. Targeted therapy selects for SOX10 knockout cells underscoring their drug tolerant properties. Combining cIAP1/2 inhibitor with BRAF/MEK inhibitors delays the onset of acquired resistance in melanomas in vivo. These data suggest that SOX10 mediates phenotypic switching in cutaneous melanoma to produce a targeted inhibitor tolerant state that is likely a prelude to the acquisition of resistance. Furthermore, we provide a therapeutic strategy to selectively eliminate SOX10-deficient cells.

Published
2021

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