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Your search keyword '"Charles F. Voliva"' showing total 17 results
Start Over Author "Charles F. Voliva" Publisher american association for cancer research (aacr)
17 results on '"Charles F. Voliva"'

1. Supplemental Figure S1 from RAF-Mutant Melanomas Differentially Depend on ERK2 Over ERK1 to Support Aberrant MAPK Pathway Activation and Cell Proliferation

Author

Alyson K. Freeman, Darrin D. Stuart, Jeffery A. Engelman, Daniel P. Rakiec, David A. Ruddy, Yanqun Wang, Matthew D. Shirley, Charles F. Voliva, Tatiana Zavorotinskaya, and Matthew S. Crowe

Abstract

Supplementary Figure S1 shows genetic dependency profiles for BRAF, MAPK1 (ERK2), and MAPK3 (ERK1) by BRAFV600 mutation status from three independent screens: DRIVE, ACHILLES, and AVANA.

Published
2023
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2. Supplementary Figure 8 from Identification and Characterization of NVP-BKM120, an Orally Available Pan-Class I PI3-Kinase Inhibitor

Author

Charles F. Voliva, William R. Sellers, Carlos García-Echeverría, Francesco Hofmann, Robert Schlegel, Christopher J. Wilson, Doriano Fabbro, Georg Martiny-Baron, Daniel Menezes, Alain De Pover, Kevin Shoemaker, Patrick Chène, Marion Dorsch, Christine Fritsch, Saskia Brachmann, Marion Wiesmann, Tobi Nagel, Daniel Guthy, Christian Schnell, Dario Sterker, Mark Knapp, Matthew Burger, Alan Huang, Sabina Pecchi, and Sauveur-Michel Maira

Abstract

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Published
2023
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3. Supplementary Figure 6 from Identification and Characterization of NVP-BKM120, an Orally Available Pan-Class I PI3-Kinase Inhibitor

Author

Charles F. Voliva, William R. Sellers, Carlos García-Echeverría, Francesco Hofmann, Robert Schlegel, Christopher J. Wilson, Doriano Fabbro, Georg Martiny-Baron, Daniel Menezes, Alain De Pover, Kevin Shoemaker, Patrick Chène, Marion Dorsch, Christine Fritsch, Saskia Brachmann, Marion Wiesmann, Tobi Nagel, Daniel Guthy, Christian Schnell, Dario Sterker, Mark Knapp, Matthew Burger, Alan Huang, Sabina Pecchi, and Sauveur-Michel Maira

Abstract

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Published
2023
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5. Supplemental Figure S4 from RAF-Mutant Melanomas Differentially Depend on ERK2 Over ERK1 to Support Aberrant MAPK Pathway Activation and Cell Proliferation

Author

Alyson K. Freeman, Darrin D. Stuart, Jeffery A. Engelman, Daniel P. Rakiec, David A. Ruddy, Yanqun Wang, Matthew D. Shirley, Charles F. Voliva, Tatiana Zavorotinskaya, and Matthew S. Crowe

Abstract

Supplementary Figure S4 shows Western blot analysis and dose-response effects of ERK inhibition in A375 cells expressing inhibitor-resistant ERK2 with or without additional mutations affecting kinase activity or substrate docking.

Published
2023
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6. Supplementary Figure 3 from Identification and Characterization of NVP-BKM120, an Orally Available Pan-Class I PI3-Kinase Inhibitor

Author

Charles F. Voliva, William R. Sellers, Carlos García-Echeverría, Francesco Hofmann, Robert Schlegel, Christopher J. Wilson, Doriano Fabbro, Georg Martiny-Baron, Daniel Menezes, Alain De Pover, Kevin Shoemaker, Patrick Chène, Marion Dorsch, Christine Fritsch, Saskia Brachmann, Marion Wiesmann, Tobi Nagel, Daniel Guthy, Christian Schnell, Dario Sterker, Mark Knapp, Matthew Burger, Alan Huang, Sabina Pecchi, and Sauveur-Michel Maira

Abstract

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Published
2023
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8. Supplementary Figure 4 from Identification and Characterization of NVP-BKM120, an Orally Available Pan-Class I PI3-Kinase Inhibitor

Author

Charles F. Voliva, William R. Sellers, Carlos García-Echeverría, Francesco Hofmann, Robert Schlegel, Christopher J. Wilson, Doriano Fabbro, Georg Martiny-Baron, Daniel Menezes, Alain De Pover, Kevin Shoemaker, Patrick Chène, Marion Dorsch, Christine Fritsch, Saskia Brachmann, Marion Wiesmann, Tobi Nagel, Daniel Guthy, Christian Schnell, Dario Sterker, Mark Knapp, Matthew Burger, Alan Huang, Sabina Pecchi, and Sauveur-Michel Maira

Abstract

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Published
2023
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9. Supplementary Figure 7 from Identification and Characterization of NVP-BKM120, an Orally Available Pan-Class I PI3-Kinase Inhibitor

Author

Charles F. Voliva, William R. Sellers, Carlos García-Echeverría, Francesco Hofmann, Robert Schlegel, Christopher J. Wilson, Doriano Fabbro, Georg Martiny-Baron, Daniel Menezes, Alain De Pover, Kevin Shoemaker, Patrick Chène, Marion Dorsch, Christine Fritsch, Saskia Brachmann, Marion Wiesmann, Tobi Nagel, Daniel Guthy, Christian Schnell, Dario Sterker, Mark Knapp, Matthew Burger, Alan Huang, Sabina Pecchi, and Sauveur-Michel Maira

Abstract

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Published
2023
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10. Supplemental Figure S3 from RAF-Mutant Melanomas Differentially Depend on ERK2 Over ERK1 to Support Aberrant MAPK Pathway Activation and Cell Proliferation

Author

Alyson K. Freeman, Darrin D. Stuart, Jeffery A. Engelman, Daniel P. Rakiec, David A. Ruddy, Yanqun Wang, Matthew D. Shirley, Charles F. Voliva, Tatiana Zavorotinskaya, and Matthew S. Crowe

Abstract

Supplementary Figure S3 shows overexpression of MAPK1 (ERK2) in human melanoma cell lines compared to MAPK3 (ERK1) and cell lines of other lineages, a correlation of ERK2 dependency with MAPK1 (ERK2) mRNA expression, and ERK1/2 protein expression across a select panel of cell lines.

Published
2023
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11. Supplementary Figure 2 from Identification and Characterization of NVP-BKM120, an Orally Available Pan-Class I PI3-Kinase Inhibitor

Author

Charles F. Voliva, William R. Sellers, Carlos García-Echeverría, Francesco Hofmann, Robert Schlegel, Christopher J. Wilson, Doriano Fabbro, Georg Martiny-Baron, Daniel Menezes, Alain De Pover, Kevin Shoemaker, Patrick Chène, Marion Dorsch, Christine Fritsch, Saskia Brachmann, Marion Wiesmann, Tobi Nagel, Daniel Guthy, Christian Schnell, Dario Sterker, Mark Knapp, Matthew Burger, Alan Huang, Sabina Pecchi, and Sauveur-Michel Maira

Abstract

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Published
2023
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12. Data from RAF-Mutant Melanomas Differentially Depend on ERK2 Over ERK1 to Support Aberrant MAPK Pathway Activation and Cell Proliferation

Author

Alyson K. Freeman, Darrin D. Stuart, Jeffery A. Engelman, Daniel P. Rakiec, David A. Ruddy, Yanqun Wang, Matthew D. Shirley, Charles F. Voliva, Tatiana Zavorotinskaya, and Matthew S. Crowe

Abstract

Half of advanced human melanomas are driven by mutant BRAF and dependent on MAPK signaling. Interestingly, the results of three independent genetic screens highlight a dependency of BRAF-mutant melanoma cell lines on BRAF and ERK2, but not ERK1. ERK2 is expressed higher in melanoma compared with other cancer types and higher than ERK1 within melanoma. However, ERK1 and ERK2 are similarly required in primary human melanocytes transformed with mutant BRAF and are expressed at a similar, lower amount compared with established cancer cell lines. ERK1 can compensate for ERK2 loss as seen by expression of ERK1 rescuing the proliferation arrest mediated by ERK2 loss (both by shRNA or inhibition by an ERK inhibitor). ERK2 knockdown, as opposed to ERK1 knockdown, led to more robust suppression of MAPK signaling as seen by RNA-sequencing, qRT-PCR, and Western blot analysis. In addition, treatment with MAPK pathway inhibitors led to gene expression changes that closely resembled those seen upon knockdown of ERK2 but not ERK1. Together, these data demonstrate that ERK2 drives BRAF-mutant melanoma gene expression and proliferation as a function of its higher expression compared with ERK1. Selective inhibition of ERK2 for the treatment of melanomas may spare the toxicity associated with pan-ERK inhibition in normal tissues.Implications:BRAF-mutant melanomas overexpress and depend on ERK2 but not ERK1, suggesting that ERK2-selective inhibition may be toxicity sparing.

Published
2023
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13. Supplementary Figure 1 from Identification and Characterization of NVP-BKM120, an Orally Available Pan-Class I PI3-Kinase Inhibitor

Author

Charles F. Voliva, William R. Sellers, Carlos García-Echeverría, Francesco Hofmann, Robert Schlegel, Christopher J. Wilson, Doriano Fabbro, Georg Martiny-Baron, Daniel Menezes, Alain De Pover, Kevin Shoemaker, Patrick Chène, Marion Dorsch, Christine Fritsch, Saskia Brachmann, Marion Wiesmann, Tobi Nagel, Daniel Guthy, Christian Schnell, Dario Sterker, Mark Knapp, Matthew Burger, Alan Huang, Sabina Pecchi, and Sauveur-Michel Maira

Abstract

PDF file - 419K

Published
2023
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14. Supplementary Materials, Tables 1-2, Figure Legends 1-8 from Identification and Characterization of NVP-BKM120, an Orally Available Pan-Class I PI3-Kinase Inhibitor

Author

Charles F. Voliva, William R. Sellers, Carlos García-Echeverría, Francesco Hofmann, Robert Schlegel, Christopher J. Wilson, Doriano Fabbro, Georg Martiny-Baron, Daniel Menezes, Alain De Pover, Kevin Shoemaker, Patrick Chène, Marion Dorsch, Christine Fritsch, Saskia Brachmann, Marion Wiesmann, Tobi Nagel, Daniel Guthy, Christian Schnell, Dario Sterker, Mark Knapp, Matthew Burger, Alan Huang, Sabina Pecchi, and Sauveur-Michel Maira

Abstract

PDF file - 180K

Published
2023
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15. Supplementary Figure 5 from Identification and Characterization of NVP-BKM120, an Orally Available Pan-Class I PI3-Kinase Inhibitor

Author

Charles F. Voliva, William R. Sellers, Carlos García-Echeverría, Francesco Hofmann, Robert Schlegel, Christopher J. Wilson, Doriano Fabbro, Georg Martiny-Baron, Daniel Menezes, Alain De Pover, Kevin Shoemaker, Patrick Chène, Marion Dorsch, Christine Fritsch, Saskia Brachmann, Marion Wiesmann, Tobi Nagel, Daniel Guthy, Christian Schnell, Dario Sterker, Mark Knapp, Matthew Burger, Alan Huang, Sabina Pecchi, and Sauveur-Michel Maira

Abstract

PDF file - 532K

Published
2023
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16. Supplemental Figure S5 from RAF-Mutant Melanomas Differentially Depend on ERK2 Over ERK1 to Support Aberrant MAPK Pathway Activation and Cell Proliferation

Author

Alyson K. Freeman, Darrin D. Stuart, Jeffery A. Engelman, Daniel P. Rakiec, David A. Ruddy, Yanqun Wang, Matthew D. Shirley, Charles F. Voliva, Tatiana Zavorotinskaya, and Matthew S. Crowe

Abstract

Supplementary Figure S5 shows mRNA microarray data from WM266-4 cells upon knockdown of ERK1 or ERK2 or treatment with MAPK inhibitors as well as detailed analysis of RNAseq data and RT-PCR validation from A375 cells with knockdown of ERK1 or ERK2 or with knockdown of ERK2 and exogenous overexpression of ERK1.

Published
2023
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17. Abstract 1140: A novel MTA non-competitive PRMT5 inhibitor

Author

Matt Soars, Lisa M. Kopcho, Carolyn A. Weigelt, Shilpa Demes, Gregory D. Vite, Mary J. Harner, Rohit Malik, Guo Li, David G. Harden, Charles F. Voliva, Kevin O’Malley, Zheming Ruan, Lan-Ying Qin, Brian J. Arey, Peter K. Park, Jennifer Price, Steven Sheriff, Gerald J. Duke, Ashvinikumar V. Gavai, JIngjing Deng, Brian E. Fink, Christopher M. Barbieri, Max Ruzanov, Muge Celiktas, Mark R. Witmer, Yuval Blat, William D. Schmitz, Joseph G. Naglich, and Iyoncy Rodrigo

Subjects
Cancer Research, Gene knockdown, Chemistry, Protein arginine methyltransferase 5, Cancer, medicine.disease, Molecular biology, In vitro, law.invention, Oncology, CDKN2A, In vivo, law, Cancer cell, medicine, Suppressor
Abstract

The chromosome 9p21 (chr9p21) locus is deleted in almost 10% of all cancer types. This locus includes the CDKN2A gene that encodes the critical tumor suppressors p19-ARF and p16-INK4a. Methylthioadenosine phosphorylase (MTAP), a gene proximal to CDKN2A, is co-deleted in 80%-90% of tumors with CDKN2A deletion. MTAP plays a critical role in the methionine salvage pathway, and the deletion of MTAP results in the accumulation of its substrate methythioadenosine (MTA). Accumulation of MTA partially inhibits the activity of the arginine methyltransferase PRMT5, causing MTAP deficient cancer cells to be more sensitive to the genetic knockdown of PRMT5. In contrast to genetic knockdown, sensitivity to pharmacological inhibition of PRMT5 does not appear to stratify with MTAP status. However, currently known PRMT5 inhibitors all possess SAM competitive or uncompetitive MOIs, which generally require displacement of MTA from the active site for binding. We hypothesize that leveraging the high MTA state induced by MTAP deficiency will require an inhibitor that can bind PRMT5 without disrupting bound MTA. Here we report the discovery of a PRMT5 inhibitor with a novel binding mode that is compatible with MTA binding. While this compound possesses the desired MOI, it shows only modestly increased potency toward MTAP-null cells. Mathematical simulations of different inhibitor mechanisms indicate that the degree of selectivity that can be achieved depends on the difference in MTA levels between MTAP-null and WT cells. Our in vitro data suggest that the elevation in intracellular MTA concentrations that occurs with MTAP deletion is not sufficient to confer significantly increased sensitivity to PRMT5 inhibition. We anticipate that the therapeutic index that can be achieved between MTAP-null tumor cells and PRMT5-sensitive normal tissues will be similarly limited in vivo. Citation Format: Rohit Malik, Peter K. Park, Christopher M. Barbieri, Yuval Blat, Steven Sheriff, Carolyn A. Weigelt, Lisa M. Kopcho, Muge Celiktas, Max Ruzanov, Joseph G. Naglich, Jennifer L. Price, Mary Harner, Kevin M. Omalley, JIngjing Deng, William Schmitz, Guo Li, Zheming Ruan, Lan-ying Qin, Gerald J. Duke, Iyoncy Rodrigo, Mark R. Witmer, David G. Harden, Shilpa Demes, Brian J. Arey, Matt Soars, Brian E. Fink, Ashvinikumar V. Gavai, Gregory D. Vite, Charles F. Voliva. A novel MTA non-competitive PRMT5 inhibitor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1140.

Published
2021
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