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Your search keyword '"Wulf, Gerburg"' showing total 6 results
Start Over Author "Wulf, Gerburg" Journal nature communications
6 results on '"Wulf, Gerburg"'

1. Reciprocal antagonism of PIN1-APC/CCDH1 governs mitotic protein stability and cell cycle entry

Author

Ke, Shizhong, Dang, Fabin, Wang, Lin, Chen, Jia-Yun, Naik, Mandar T., Li, Wenxue, Thavamani, Abhishek, Kim, Nami, Naik, Nandita M., Sui, Huaxiu, Tang, Wei, Qiu, Chenxi, Koikawa, Kazuhiro, Batalini, Felipe, Stern Gatof, Emily, Isaza, Daniela Arango, Patel, Jaymin M., Wang, Xiaodong, Clohessy, John G., Heng, Yujing J., Lahav, Galit, Liu, Yansheng, Gray, Nathanael S., Zhou, Xiao Zhen, Wei, Wenyi, Wulf, Gerburg M., and Lu, Kun Ping

Published
2024
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4. MAT2A inhibitor AG-270/S095033 in patients with advanced malignancies: a phase I trial.

Author

Gounder, Mrinal, Johnson, Melissa, Heist, Rebecca S., Shapiro, Geoffrey I., Postel-Vinay, Sophie, Wilson, Frederick H., Garralda, Elena, Wulf, Gerburg, Almon, Caroline, Nabhan, Salah, Aguado-Fraile, Elia, He, Peng, Romagnoli, Mathilde, Hossain, Mohammad, Narayanaswamy, Rohini, Sadou-Dubourgnoux, Amel, Cooper, Michael, Askoxylakis, Vasileios, Burris, Howard A., and Tabernero, Josep

Subjects
LIVER function tests, ADENOSYLMETHIONINE, PHARMACOKINETICS, METHIONINE, THROMBOCYTOPENIA
Abstract

Homozygous MTAP deletion occurs in ~15% of cancers, making them vulnerable to decreases in the concentration of S-adenosylmethionine (SAM). AG-270/S095033 is an oral, potent, reversible inhibitor of methionine adenosyltransferase 2 A (MAT2A), the enzyme primarily responsible for the synthesis of SAM. We report results from the first-in-human, phase 1 trial of AG-270/S095033 as monotherapy in patients with advanced malignancies (ClinicalTrials.gov Identifier: NCT03435250). Eligible patients had tumors with homozygous deletion of CDKN2A/MTAP and/or loss of MTAP protein by immunohistochemistry. Patients received AG-270/S095033 once daily (QD) or twice daily (BID) in 28-day cycles. The primary objective was to assess the maximum tolerated dose (MTD) of AG-270/S095033. Secondary objectives included safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy. Forty patients were treated with AG-270/S095033. Plasma concentrations of AG-270/S095033 increased with dose. Maximal reductions in plasma SAM concentrations ranged from 54% to 70%. Analysis of paired tumor biopsies showed decreases in levels of symmetrically di-methylated arginine (SDMA) residues. Reversible increases in liver function tests, thrombocytopenia, anemia and fatigue were common treatment-related toxicities. Two partial responses were observed; five additional patients achieved radiographically confirmed stable disease for ≥16 weeks. AG-270/S095033 has a manageable safety profile. Our data provide preliminary evidence of clinical activity and proof-of-mechanism for MAT2A inhibition. AG-270 inhibited the activity of MAT2A and reduced plasma concentrations of SAM by up to 70% in patients with advanced solid tumors. Partial responses were observed in two patients and disease stabilization for ≥4 months was seen in five patients. [ABSTRACT FROM AUTHOR]

Published
2025
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5. Molecular correlates of response to eribulin and pembrolizumab in hormone receptor-positive metastatic breast cancer

Author

Keenan, Tanya E., Guerriero, Jennifer L., Barroso-Sousa, Romualdo, Li, Tianyu, O’Meara, Tess, Giobbie-Hurder, Anita, Tayob, Nabihah, Hu, Jiani, Severgnini, Mariano, Agudo, Judith, Vaz-Luis, Ines, Anderson, Leilani, Attaya, Victoria, Park, Jihye, Conway, Jake, He, Meng Xiao, Reardon, Brendan, Shannon, Erin, Wulf, Gerburg, Spring, Laura M., Jeselsohn, Rinath, Krop, Ian, Lin, Nancy U., Partridge, Ann, Winer, Eric P., Mittendorf, Elizabeth A., Liu, David, Van Allen, Eliezer M., and Tolaney, Sara M.

Published
2021
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