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Your search keyword '"Wechsler-Reya, Robert J."' showing total 8 results
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8 results on '"Wechsler-Reya, Robert J."'

1. Early rhombic lip Protogenin+ve stem cells in a human-specific neurovascular niche initiate and maintain group 3 medulloblastoma

Author

Visvanathan, Abhirami, Saulnier, Olivier, Chen, Chuan, Haldipur, Parthiv, Orisme, Wilda, Delaidelli, Alberto, Shin, Seungmin, Millman, Jake, Bryant, Andrew, Abeysundara, Namal, Wu, Xujia, Hendrikse, Liam D., Patil, Vikas, Bashardanesh, Zahedeh, Golser, Joseph, Livingston, Bryn G., Nakashima, Takuma, Funakoshi, Yusuke, Ong, Winnie, Rasnitsyn, Alexandra, Aldinger, Kimberly A., Richman, Cory M., Van Ommeren, Randy, Lee, John J.Y., Ly, Michelle, Vladoiu, Maria C., Kharas, Kaitlin, Balin, Polina, Erickson, Anders W., Fong, Vernon, Zhang, Jiao, Suárez, Raúl A., Wang, Hao, Huang, Ning, Pallota, Jonelle G., Douglas, Tajana, Haapasalo, Joonas, Razavi, Ferechte, Silvestri, Evelina, Sirbu, Olga, Worme, Samantha, Kameda-Smith, Michelle M., Wu, Xiaochong, Daniels, Craig, MichaelRaj, Antony K., Bhaduri, Aparna, Schramek, Daniel, Suzuki, Hiromichi, Garzia, Livia, Ahmed, Nabil, Kleinman, Claudia L., Stein, Lincoln D., Dirks, Peter, Dunham, Christopher, Jabado, Nada, Rich, Jeremy N., Li, Wei, Sorensen, Poul H., Wechsler-Reya, Robert J., Weiss, William A., Millen, Kathleen J., Ellison, David W., Dimitrov, Dimiter S., and Taylor, Michael D.

Published
2024
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2. Just a spoonful of metformin helps the medicine go down

Author

Tzaridis, Theophilos and Wechsler-Reya, Robert J.

Subjects
Drug therapy, Combination -- Health aspects, Brain tumors -- Health aspects, Hypoglycemic agents -- Health aspects, Hyperglycemia -- Health aspects, Health care industry
Abstract

Diffuse intrinsic pontine glioma (DIPG) is a devastating brain tumor with a need for novel therapies. So far, monotherapies have failed to prolong survival for these patients, and combinatorial strategies have often shown severe, dose-limiting toxicities. In this issue of the JCI, Duchatel, Jackson, and colleagues address this challenge by introducing a drug combination that mitigates side effects and overcomes resistance. After identifying the PI3K/mTOR pathway as a therapeutic vulnerability, they treated DIPG-bearing mice with paxalisib and saw responses but also observed hyperglycemia as a severe side effect. Combining paxalisib with metformin mitigated this toxicity, but also upregulated protein kinase C (PKC) signaling. To tackle this mechanism of resistance, the authors added the PKC inhibitor enzastaurin to their drug combination and showed that this triple therapy led to improved survival. This approach paves the way for improved outcomes for patients with DIPG and other brain tumors., Balancing safety and efficacy in treatment of DIPG The Swiss physician and philosopher Paracelsus famously said, 'All things are poison and nothing is without poison. Solely the dose determines that [...]

Published
2024
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4. Elucidation and Pharmacologic Targeting of Master Regulator Dependencies in Coexisting Diffuse Midline Glioma Subpopulations

Author

Fernández, Ester Calvo, primary, Tomassoni, Lorenzo, additional, Zhang, Xu, additional, Wang, Junqiang, additional, Obradovic, Aleksandar, additional, Laise, Pasquale, additional, Griffin, Aaron T., additional, Vlahos, Lukas, additional, Minns, Hanna E., additional, Morales, Diana V., additional, Simmons, Christian, additional, Gallitto, Matthew, additional, Wei, Hong-Jian, additional, Martins, Timothy J., additional, Becker, Pamela S., additional, Crawford, John R., additional, Tzaridis, Theophilos, additional, Wechsler-Reya, Robert J., additional, Garvin, James, additional, Gartrell, Robyn D., additional, Szalontay, Luca, additional, Zacharoulis, Stergios, additional, Wu, Cheng-Chia, additional, Zhang, Zhiguo, additional, Califano, Andrea, additional, and Pavisic, Jovana, additional

Published
2024
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5. Developmental basis of SHH medulloblastoma heterogeneity

Author

Gold, Maxwell P., primary, Ong, Winnie, additional, Masteller, Andrew M., additional, Ghasemi, David R., additional, Galindo, Julie Anne, additional, Park, Noel R., additional, Huynh, Nhan C., additional, Donde, Aneesh, additional, Pister, Veronika, additional, Saurez, Raul A., additional, Vladoiu, Maria C., additional, Hwang, Grace H., additional, Eisemann, Tanja, additional, Donovan, Laura K., additional, Walker, Adam D., additional, Benetatos, Joseph, additional, Dufour, Christelle, additional, Garzia, Livia, additional, Segal, Rosalind A., additional, Wechsler-Reya, Robert J., additional, Mesirov, Jill P., additional, Korshunov, Andrey, additional, Pajtler, Kristian W., additional, Pomeroy, Scott L., additional, Ayrault, Olivier, additional, Davidson, Shawn M., additional, Cotter, Jennifer A., additional, Taylor, Michael D., additional, and Fraenkel, Ernest, additional

Published
2024
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6. A road map for the treatment of pediatric diffuse midline glioma

Author

Koschmann, Carl, Al-Holou, Wajd N., Alonso, Marta M., Anastas, Jamie, Bandopadhayay, Pratiti, Barron, Tara, Becher, Oren, Cartaxo, Rodrigo, Castro, Maria G., Chung, Chan, Clausen, Madison, Dang, Derek, Doherty, Robert, Duchatel, Ryan, Dun, Matthew, Filbin, Mariella, Franson, Andrea, Galban, Stefanie, Garcia Moure, Marc, Garton, Hugh, Gowda, Pruthvi, Marques, Joana Graca, Hawkins, Cynthia, Heath, Allison, Hulleman, Esther, Ji, Sunjong, Jones, Chris, Kilburn, Lindsay, Kline, Cassie, Koldobskiy, Michael A., Lim, Daniel, Lowenstein, Pedro R., Lu, Q. Richard, Lum, Joanna, Mack, Stephen, Magge, Suresh, Marini, Bernard, Martin, Donna, Marupudi, Neena, Messinger, Dana, Mody, Rajen, Morgan, Meredith, Mota, Mateus, Muraszko, Karin, Mueller, Sabine, Natarajan, Siva Kumar, Nazarian, Javad, Niculcea, Michael, Nuechterlein, Nicholas, Okada, Hideho, Opipari, Valerie, Pai, Manjunath P., Pal, Sharmistha, Peterson, Erik, Phoenix, Timothy, Prensner, John R., Pun, Matthew, Raju, G. Praveen, Reitman, Zachary J., Resnick, Adam, Rogawski, David, Saratsis, Amanda, Sbergio, Stefanie G., Souweidane, Mark, Stafford, James M., Tzaridis, Theophilos, Venkataraman, Sujatha, Vittorio, Orazio, Wadden, Jack, Wahl, Daniel, Wechsler-Reya, Robert J., Yadav, Viveka Nand, Zhang, Xu, Zhang, Qiang, and Venneti, Sriram

Published
2024
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7. The Virtual Child.

Author

Gilbertson RJ, Behjati S, Böttcher AL, Bronner ME, Burridge M, Clausing H, Clifford H, Danaher T, Donovan LK, Drost J, Eggermont AMM, Emerson C, Flores MG, Hamerlik P, Jabado N, Jones A, Kaessmann H, Kleinman CL, Kool M, Kutscher LM, Lindberg G, Linnane E, Marioni JC, Maris JM, Monje M, Macaskill A, Niederer S, Northcott PA, Peeters E, Plieger-van Solkema W, Preußner L, Rios AC, Rippe K, Sandford P, Sgourakis NG, Shlien A, Smith P, Straathof K, Sullivan PJ, Suvà ML, Taylor MD, Thompson E, Vento-Tormo R, Wainwright BJ, Wechsler-Reya RJ, Westermann F, Winslade S, Al-Lazikani B, and Pfister SM

Subjects
Humans, Neoplasms genetics
Abstract

Summary: We are building the world's first Virtual Child-a computer model of normal and cancerous human development at the level of each individual cell. The Virtual Child will "develop cancer" that we will subject to unlimited virtual clinical trials that pinpoint, predict, and prioritize potential new treatments, bringing forward the day when no child dies of cancer, giving each one the opportunity to lead a full and healthy life., (©2024 American Association for Cancer Research.)

Published
2024
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8. Elucidation and Pharmacologic Targeting of Master Regulator Dependencies in Coexisting Diffuse Midline Glioma Subpopulations.

Author

Fernández EC, Tomassoni L, Zhang X, Wang J, Obradovic A, Laise P, Griffin AT, Vlahos L, Minns HE, Morales DV, Simmons C, Gallitto M, Wei HJ, Martins TJ, Becker PS, Crawford JR, Tzaridis T, Wechsler-Reya RJ, Garvin J, Gartrell RD, Szalontay L, Zacharoulis S, Wu CC, Zhang Z, Califano A, and Pavisic J

Abstract

Diffuse Midline Gliomas (DMGs) are universally fatal, primarily pediatric malignancies affecting the midline structures of the central nervous system. Despite decades of clinical trials, treatment remains limited to palliative radiation therapy. A major challenge is the coexistence of molecularly distinct malignant cell states with potentially orthogonal drug sensitivities. To address this challenge, we leveraged established network-based methodologies to elucidate Master Regulator (MR) proteins representing mechanistic, non-oncogene dependencies of seven coexisting subpopulations identified by single-cell analysis-whose enrichment in essential genes was validated by pooled CRISPR/Cas9 screens. Perturbational profiles of 372 clinically relevant drugs helped identify those able to invert the activity of subpopulation-specific MRs for follow-up in vivo validation. While individual drugs predicted to target individual subpopulations-including avapritinib, larotrectinib, and ruxolitinib-produced only modest tumor growth reduction in orthotopic models, systemic co-administration induced significant survival extension, making this approach a valuable contribution to the rational design of combination therapy.

Published
2024
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