Disordered methionine metabolism in MTAP/CDKN2A-deleted cancers leads to dependence on PRMT5

Mavrakis, Konstantinos J.; McDonald, E. Robert; Schlabach, Michael R.; Billy, Eric; Hoffman, Gregory R.; deWeck, Antoine; Ruddy, David A.; Venkatesan, Kavitha; Yu, Jianjun; McAllister, Gregg; Stump, Mark; deBeaumont, Rosalie; Ho, Samuel; Yue, Yingzi; Liu, Yue; Yan-Neale, Yan; Yang, Guizhi; Lin, Fallon; Yin, Hong; Gao, Hui; Kipp, D. Randal; Zhao, Songping; McNamara, Joshua T.; Sprague, Elizabeth R.; Zheng, Bing; Lin, Ying; Cho, Young Shin; Gu, Justin; Crawford, Kenneth; Ciccone, David; Vitari, Alberto C.; Lai, Albert; Capka, Vladimir; Hurov, Kristen; Porter, Jeffery A.; Tallarico, John; Mickanin, Craig; Lees, Emma; Pagliarini, Raymond; Keen, Nicholas; Schmelzle, Tobias; Hofmann, Francesco; Stegmeier, Frank; Sellers, William R.

doi:10.1126/science.aad5944

Cited by 623Cancer-related gene regulationRNA modifications and cancerBiochemical and Molecular Research

Disordered methionine metabolism in MTAP/CDKN2A-deleted cancers leads to dependence on PRMT5

Mavrakis, Konstantinos J., McDonald, E. Robert, Schlabach, Michael R., Billy, Eric, Hoffman, Gregory R., deWeck, Antoine, Ruddy, David A., Venkatesan, Kavitha +36 more·2016·Science

DOI 10.1126/science.aad5944

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Abstract

Tumors put in a vulnerable position: Cancer cells often display alterations in metabolism that help fuel their growth. Such metabolic “rewiring” may also work against the cancer cells, however, by creating new vulnerabilities that can be exploited therapeutically. A variety of human tumors show changes in methionine metabolism caused by loss of the gene coding for 5-methylthioadenosine phosphorylase (MTAP). Mavrakis et al. and Kryukov et al. found that the loss of MTAP renders cancer cell lines sensitive to growth inhibition by compounds that suppress the activity of a specific arginine methyltransferase called PRMT5. Conceivably, drugs that inhibit PRMT5 activity could be developed into a tailored therapy for MTAP-deficient tumors. Science , this issue pp. 1208 and 1214

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Loss of MTAP causes MTA to accumulate, and this MTA can inhibit PRMT5, creating a vulnerability in cancer cells.
“Loss of MTAP expression can result in another vulnerability for cancer cells because the MTA that accumulates following MTAP loss can act as a potent inhibitor of the enzyme arginine methyltransferase 5 (PRMT5).”
From Targeting Metabolism for Cancer Therapy (2017) · cites this paper as Mavrakis et al., 2016
Deletion of CDKN2A results in concomitant deletion of MTAP in many cancers, including 53% of glioblastomas and 26% of pancreatic cancers.
“Deletion of the tumor suppressor CDKN2A results in concomitant deletion of the methionine salvage pathway enzyme methylthioadenosine phosphorylase (MTAP) in many cancers, including 53% of glioblastomas and 26% of pancreatic cancers (Mavrakis et al., 2016).”
From Targeting Metabolism for Cancer Therapy (2017) · cites this paper as Mavrakis et al., 2016
MTAP-null cancer cells are more sensitive to PRMT5 depletion than isogenic cancer cells that express MTAP.
“MTAP loss results in reduced PRMT5 activity and renders MTAP-null cancer cell more sensitive to PRMT5 depletion than isogenic counterparts that express MTAP (Kryukov et al., 2016; Marjon et al., 2016; Mavrakis et al., 2016).”
From Targeting Metabolism for Cancer Therapy (2017) · cites this paper as Mavrakis et al., 2016

Features and development of Coot
Emsley, P., Lohkamp, B., Scott, W. G., & Cowtan, K. D. (2010) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444910007493 · Cited by 27,510 · see citing works
Overview of the CCP 4 suite and current developments
Winn, M. D., Ballard, C. C., Cowtan, K. D., Dodson, E. J., Emsley, P., Evans, P. R., Keegan, R. M., Krissinel, E. B., Leslie, A. G. W., McCoy, A., et al. (2011) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444910045749 · Cited by 12,353 · see citing works
The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity
Barretina, J., Caponigro, G., Stransky, N., Venkatesan, K., Margolin, A. A., Kim, S., Wilson, C. J., Lehár, J., Kryukov, G. V., Sonkin, D., et al. (2012) · Nature · doi:10.1038/nature11003 · Cited by 7,950 · see citing works
Self-citation
How good are my data and what is the resolution?
Evans, P. R., & Murshudov, G. N. (2013) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444913000061 · Cited by 4,747 · see citing works
Genetic screens in human cells using the CRISPR-Cas9 system
Wang, T., Wei, J. J., Sabatini, D. M., & Lander, E. S. (2014) · Science · doi:10.1126/science.1246981 · Cited by 2,856 · see citing works
Data processing and analysis with the autoPROC toolbox
Vonrhein, C., Flensburg, C., Keller, P., Sharff, A., Smart, O. S., Paciorek, W. A., Womack, T. O., & Bricogne, G. (2011) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444911007773 · Cited by 2,084 · see citing works
An introduction to data reduction: space-group determination, scaling and intensity statistics
Evans, P. R. (2011) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s090744491003982x · Cited by 1,507 · see citing works
MTAP deletion confers enhanced dependency on the PRMT5 arginine methyltransferase in cancer cells
Kryukov, G. V., Wilson, F. H., Ruth, J. R., Paulk, J., Tsherniak, A., Marlow, S. E., Vazquez, F., Weir, B. A., Fitzgerald, M. E., Tanaka, M., et al. (2016) · Science · doi:10.1126/science.aad5214 · Cited by 688 · see citing works
A selective inhibitor of PRMT5 with in vivo and in vitro potency in MCL models
Chan-Penebre, E., Kuplast, K. G., Majer, C. R., Boriack-Sjodin, P. A., Wigle, T. J., Johnston, L. D., Rioux, N., Munchhof, M. J., Jin, L., Jacques, S. L., et al. (2015) · Nature Chemical Biology · doi:10.1038/nchembio.1810 · Cited by 569 · see citing works
Selective inhibition of Ezh2 by a small molecule inhibitor blocks tumor cells proliferation
Qi, W., Chan, H., Teng, L., Li, L., Chuai, S., Zhang, R., Zeng, J., Li, M., Fan, H. X., Lin, Y., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1210371110 · Cited by 550 · see citing works
Self-citation
Functional epigenetics approach identifies BRM/SMARCA2 as a critical synthetic lethal target in BRG1-deficient cancers
Hoffman, G. R., Rahal, R., Buxton, F., Xiang, K., McAllister, G., Frias, E., Bagdasarian, L., Huber, J., Lindeman, A., Chen, D., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1316793111 · Cited by 421 · see citing works
Self-citation
Crystal structure of the human PRMT5:MEP50 complex
Antonysamy, S., Bonday, Z., Campbell, R. M., Doyle, B. L., Druzina, Z., Gheyi, T., Han, B., Jungheim, L. N., Qian, Y., Rauch, C. T., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1209814109 · Cited by 373 · see citing works
PRMT5 (Janus Kinase-binding Protein 1) Catalyzes the Formation of Symmetric Dimethylarginine Residues in Proteins
Branscombe, T. L., Frankel, A., Lee, J., Cook, J. R., Yang, Z.-H., Pestka, S., & Clarke, S. G. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m105412200 · Cited by 364 · see citing works
Passenger deletions generate therapeutic vulnerabilities in cancer
Muller, F. L., Colla, S., Aquilanti, E., Manzo, V. E., Genovese, G., Lee, J., Eisenson, D., Narurkar, R., Deng, P., Nezi, L., et al. (2012) · Nature · doi:10.1038/nature11331 · Cited by 339 · see citing works
RioK1, a New Interactor of Protein Arginine Methyltransferase 5 (PRMT5), Competes with pICln for Binding and Modulates PRMT5 Complex Composition and Substrate Specificity
Guderian, G., Peter, C., Wiesner, J., Sickmann, A., Schulze‐Osthoff, K., Fischer, U., & Grimmler, M. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.148486 · Cited by 163 · see citing works
Structure of the Arginine Methyltransferase PRMT5-MEP50 Reveals a Mechanism for Substrate Specificity
Ho, M.-C., Wilczek, C., Bonanno, J. B., Li, X., Seznec, J., Matsui, T., Carter, L. G., Onikubo, T., Kumar, P. R., Chan, M. K., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0057008 · Cited by 144 · see citing works
ATARiS: Computational quantification of gene suppression phenotypes from multisample RNAi screensPreprint
Shao, D. D., Tsherniak, A., Gopal, S., Weir, B., Tamayo, P., Stransky, N., Schumacher, S., Zack, T., Beroukhim, R., Garraway, L., et al. (2013) · Genome Research · doi:10.1101/gr.143586.112 · Cited by 124 · see citing works
Tumorigenic activity and therapeutic inhibition of Rheb GTPasePreprint
Mavrakis, K. J., Zhu, H., Silva, R. L. A., Mills, J. R., Teruya‐Feldstein, J., Lowe, S. W., Tam, W., Pelletier, J., & Wendel, H. (2008) · Genes & Development · doi:10.1101/gad.1690808 · Cited by 113 · see citing works
Self-citation
DNA sequencing and CRISPR-Cas9 gene editing for target validation in mammalian cells
Smurnyy, Y. D., Cai, M., Wu, H., McWhinnie, E. A., Tallarico, J. A., Yang, Y., & Feng, Y. (2014) · Nature Chemical Biology · doi:10.1038/nchembio.1550 · Cited by 97 · see citing works
Self-citation
Methylthioadenosine Phosphorylase Regulates Ornithine Decarboxylase by Production of Downstream Metabolites
Subhi, A. L., Diegelman, P., Porter, C. W., Tang, B., Lu, Z. J., Markham, G. D., & Kruger, W. D. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m308451200 · Cited by 95 · see citing works
A Transition State Analogue of 5′-Methylthioadenosine Phosphorylase Induces Apoptosis in Head and Neck Cancers
Basu, I., Cordovano, G., Das, I. R., Belbin, T. J., Guha, C., & Schramm, V. L. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m702287200 · Cited by 82 · see citing works
Deregulation of protein methylation in melanoma
Limm, K., Ott, C., Wallner, S., Mueller, D. W., Oefner, P. J., Hellerbrand, C., & Bosserhoff, A. (2012) · European Journal of Cancer · doi:10.1016/j.ejca.2012.11.026 · Cited by 63 · see citing works
Direct and tumor microenvironment mediated influences of 5′‐deoxy‐5′‐(methylthio)adenosine on tumor progression of malignant melanoma
Stevens, A. P., Spangler, B., Wallner, S., Kreutz, M. P., Dettmer, K., Oefner, P. J., & Bosserhoff, A. (2008) · Journal of Cellular Biochemistry · doi:10.1002/jcb.21984 · Cited by 61 · see citing works
Inhibition of the tyrosine kinase activity of the fibroblast growth factor receptor by the methyltransferase inhibitor 5'-methylthioadenosine.
Maher, P. A. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)53602-4 · Cited by 55 · see citing works
Vesicular Stomatitis Viruses Resistant to the Methylase Inhibitor Sinefungin Upregulate RNA Synthesis and Reveal Mutations That Affect mRNA Cap Methylation
Li, J., Chorba, J. S., & Whelan, S. P. J. (2007) · Journal of Virology · doi:10.1128/jvi.02681-06 · Cited by 36 · see citing works
Enzyme-Dependent Lysine Deprotonation in EZH2 Catalysis
Kipp, D. R., Quinn, C. M., & Fortin, P. D. (2013) · Biochemistry · doi:10.1021/bi400805w · Cited by 19 · see citing works
Self-citation
Salvage of 5′-deoxy-methylthioadenosine into purines and methionine by lymphoid cells and inhibition of cell proliferation
Christa, L., Thuillier, L., Munier, A., & Pérignon, J. (1984) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/0167-4889(84)90048-x · Cited by 12 · see citing works
Methylthioadenosine toxicity and metabolism to methionine in mammalian cells
Christa, L., Kersual, J., Augé, J., & Pérignon, J. L. (1988) · Biochemical Journal · doi:10.1042/bj2550145 · Cited by 9 · see citing works
Full utilization of a mass spectrometer using on‐demand sharing with multiple LC units
Li, S., Hao, Q., Gounarides, J., & Wang, Y. K. (2012) · Journal of Mass Spectrometry · doi:10.1002/jms.3061 · Cited by 6 · see citing works

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Heiden, M. G. V., & DeBerardinis, R. J. (2017) · Cell · doi:10.1016/j.cell.2016.12.039 · Cited by 2,316 · see citing works
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Blanc, R. S., & Richard, S. (2017) · Molecular Cell · doi:10.1016/j.molcel.2016.11.003 · Cited by 1,054 · see citing works
Targeting Metabolism for Cancer Therapy
Luengo, A., Gui, D. Y., & Vander Heiden, M. G. (2017) · Cell Chemical Biology · doi:10.1016/j.chembiol.2017.08.028 · Cited by 971 · see citing works
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Casero, R. A., Stewart, T. M., & Pegg, A. E. (2018) · Nature reviews. Cancer · doi:10.1038/s41568-018-0050-3 · Cited by 824 · see citing works
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Sun, L., Zhang, H., & Gao, P. (2021) · Protein & Cell · doi:10.1007/s13238-021-00846-7 · Cited by 796 · see citing works
MTAP deletion confers enhanced dependency on the PRMT5 arginine methyltransferase in cancer cells
Kryukov, G. V., Wilson, F. H., Ruth, J. R., Paulk, J., Tsherniak, A., Marlow, S. E., Vazquez, F., Weir, B. A., Fitzgerald, M. E., Tanaka, M., et al. (2016) · Science · doi:10.1126/science.aad5214 · Cited by 688 · see citing works
Project DRIVE: a compendium of cancer dependencies and synthetic lethal relationships uncovered by large-scale, deep RNAi screening
McDonald, E. R., de Weck, A., Schlabach, M. R., Billy, E., Mavrakis, K. J., Hoffman, G. R., Belur, D., Castelletti, D., Frias, E., Gampa, K., et al. (2017) · Cell · doi:10.1016/j.cell.2017.07.005 · Cited by 658 · see citing works
Self-citation
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Ben‐David, U., & Amon, A. (2019) · Nature Reviews Genetics · doi:10.1038/s41576-019-0171-x · Cited by 651 · see citing works
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Guccione, E., & Richard, S. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0155-x · Cited by 642 · see citing works
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Hmeljak, J., Sanchez-Vega, F., Hoadley, K. A., Shih, J., Stewart, C., Heiman, D., Tarpey, P., Danilova, L., Drill, E., Gibb, E. A., et al. (2018) · Cancer Discovery · doi:10.1158/2159-8290.cd-18-0804 · Cited by 618 · see citing works
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Sanderson, S. M., Gao, X., Dai, Z., & Locasale, J. W. (2019) · Nature reviews. Cancer · doi:10.1038/s41568-019-0187-8 · Cited by 572 · see citing works
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Ling, Z., Jiang, Y.-F., Ru, J.-N., Lu, J.-H., Ding, B., & Wu, J. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01569-3 · Cited by 574 · see citing works
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Lee, S. C.-W., & Abdel-Wahab, O. I. (2016) · Nature Medicine · doi:10.1038/nm.4165 · Cited by 556 · see citing works
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Reid, M. A., Dai, Z., & Locasale, J. W. (2017) · Nature Cell Biology · doi:10.1038/ncb3629 · Cited by 515 · see citing works
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Marjon, K., Cameron, M. J., Quang, P., Clasquin, M. F., Mandley, E., Kunii, K., McVay, M., Choe, S., Kernytsky, A., Gross, S., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.03.043 · Cited by 485 · see citing works
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Self-citation
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Fedoriw, A., Rajapurkar, S., O’Brien, S. W., Gerhart, S. V., Mitchell, L. H., Adams, N. D., Rioux, N., Lingaraj, T., Ribich, S. A., Pappalardi, M. B., et al. (2019) · Cancer Cell · doi:10.1016/j.ccell.2019.05.014 · Cited by 355 · see citing works
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Self-citation
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Fong, J. Y., Pignata, L., Goy, P.-A. V., Kawabata, K. C., Lee, S. C.-W., Koh, C. M., Musiani, D., Massignani, E., Kotini, A. G., Penson, A., et al. (2019) · Cancer Cell · doi:10.1016/j.ccell.2019.07.003 · Cited by 282 · see citing works
Protein arginine methyltransferases: promising targets for cancer therapy
Hwang, J. W., Cho, Y., Bae, G., Kim, S., & Kim, Y. K. (2021) · Experimental & Molecular Medicine · doi:10.1038/s12276-021-00613-y · Cited by 274 · see citing works
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Xu, J., & Richard, S. (2021) · Molecular Cell · doi:10.1016/j.molcel.2021.09.011 · Cited by 202 · see citing works
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Tsai, W.-C., Gayatri, S., Reineke, L. C., Sbardella, G., Bedford, M. T., & Lloyd, R. E. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.739573 · Cited by 195 · see citing works
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Smith, C. R., Aranda, R., Bobinski, T. P., Briere, D. M., Burns, A. C., Christensen, J. G., Clarine, J., Engstrom, L. D., Gunn, R. J., Ivetac, A., et al. (2022) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c01900 · Cited by 180 · see citing works
Patient-derived organoids in precision cancer medicine
Tong, L., Cui, W., Zhang, B., Fonseca, P., Zhao, Q. C., Zhang, P., Xu, B., Zhang, Q., Li, Z., Seashore-Ludlow, B. A., et al. (2024) · Med · doi:10.1016/j.medj.2024.08.010 · Cited by 173 · see citing works
The genomic landscape of TERT promoter wildtype-IDH wildtype glioblastoma
Diplas, B. H., He, X., Brosnan‐Cashman, J. A., Liu, H., Chen, L. H., Wang, Z., Moure, C. J., Killela, P. J., Loriaux, D. B., Lipp, E., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-04448-6 · Cited by 172 · see citing works
Targeting methyltransferase PRMT5 eliminates leukemia stem cells in chronic myelogenous leukemia
Jin, Y., Zhou, J., Xu, F., Jin, B., Cui, L., Wang, Y., Du, X., Li, J., Li, P., Ren, R., et al. (2016) · Journal of Clinical Investigation · doi:10.1172/jci85239 · Cited by 170 · see citing works
PRMT5 methylome profiling uncovers a direct link to splicing regulation in acute myeloid leukemia
Radzisheuskaya, A., Shliaha, P. V., Grinev, V. V., Lorenzini, E., Kovalchuk, S. I., Shlyueva, D., Gorshkov, V., Hendrickson, R. C., Jensen, O. N., & Helin, K. (2019) · Nature Structural & Molecular Biology · doi:10.1038/s41594-019-0313-z · Cited by 169 · see citing works
Impact of cancer metabolism on therapy resistance – Clinical implications
Gonçalves, A. C., Richiardone, E., Jorge, J., Polónia, B. R. G., Xavier, C. P. R., Salaroglio, I. C., Riganti, C., Vasconcelos, M. H., Corbet, C., & Sarmento‐Ribeiro, A. B. (2021) · Drug Resistance Updates · doi:10.1016/j.drup.2021.100797 · Cited by 170 · see citing works
Protein arginine methyltransferases: insights into the enzyme structure and mechanism at the atomic level
Tewary, S. K., Zheng, Y. G., & Ho, M. (2019) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03145-x · Cited by 158 · see citing works
Paralog knockout profiling identifies DUSP4 and DUSP6 as a digenic dependence in MAPK pathway-driven cancers
Ito, T., Young, M. J., Li, R., Jain, S. S., Wernitznig, A., Krill-Burger, J. M., Lemke, C. T., Monducci, D., Rodriguez, D. J., Chang, L., et al. (2021) · Nature Genetics · doi:10.1038/s41588-021-00967-z · Cited by 148 · see citing works
Self-citation
Metabolic Abnormalities in Glioblastoma and Metabolic Strategies to Overcome Treatment Resistance
Zhou, W., & Wahl, D. R. (2019) · Cancers · doi:10.3390/cancers11091231 · Cited by 146 · see citing works
Methionine metabolism in chronic liver diseases: an update on molecular mechanism and therapeutic implication
Li, Z., Wang, F., Liang, B., Su, Y., Sun, S., Xia, S., Shao, J., Zhang, Z., Hong, M., Zhang, F., et al. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00349-7 · Cited by 144 · see citing works
Translational genomics of nasopharyngeal cancer
Tsang, C. M., Lui, V. W. Y., Bruce, J. P., Pugh, T. J., & Lo, K. W. (2019) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2019.09.006 · Cited by 141 · see citing works
Targeting S-adenosylmethionine biosynthesis with a novel allosteric inhibitor of Mat2A
Quinlan, C. L., Kaiser, S. E., Bolaños, B., Nowlin, D., Grantner, R., Karlicek, S., Feng, J. L., Jenkinson, S. G., Freeman‐Cook, K. D., Dann, S. G., et al. (2017) · Nature Chemical Biology · doi:10.1038/nchembio.2384 · Cited by 135 · see citing works
First-in-human study of AMG 193, an MTA-cooperative PRMT5 inhibitor, in patients with MTAP-deleted solid tumors: results from phase I dose exploration
Rodon, J. A., Prenen, H., Sacher, A. G., Villalona-Calero, M. A., Penel, N., Helali, A. E., Rottey, S., Yamamoto, N., Ghiringhelli, F., Goebeler, M., et al. (2024) · Annals of Oncology · doi:10.1016/j.annonc.2024.08.2339 · Cited by 132 · see citing works
Whole-genome profiling of nasopharyngeal carcinoma reveals viral-host co-operation in inflammatory NF-κB activation and immune escape
Bruce, J. P., To, K., Lui, V. W. Y., Chung, G. T. Y., Chan, Y., Tsang, C. M., Yip, K. Y.-L., Ma, B. B. Y., Woo, J. K. S., Hui, E. P., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-24348-6 · Cited by 127 · see citing works
Self-citation
Regulation of PRMT5–MDM4 axis is critical in the response to CDK4/6 inhibitors in melanoma
AbuHammad, S., Cullinane, C. M., Martin, C., Bacolas, Z., Ward, T. A., Chen, H., Slater, A. A., Ardley, K., Kirby, L., Chan, K. T., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1901323116 · Cited by 124 · see citing works
Integrative clinical and molecular characterization of translocation renal cell carcinoma
Bakouny, Z., Sadagopan, A., Ravi, P. K., Metaferia, N. Y., Li, J., AbuHammad, S., Tang, S., Denize, T., Garner, E. R., Gao, X. Y., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2021.110190 · Cited by 123 · see citing works
Clonal architecture in mesothelioma is prognostic and shapes the tumour microenvironment
Zhang, M., Luo, J., Sun, Q., Harber, J., Dawson, A. G., Nakas, A., Busacca, S., Sharkey, A. J., Waller, D. A., Sheaff, M. T., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-21798-w · Cited by 119 · see citing works
Patient-derived head and neck cancer organoids allow treatment stratification and serve as a tool for biomarker validation and identification
Millen, R., de Kort, W. W. B., Koomen, M., van Son, G. J. F., Gobits, R., de Vries, B. B. L. P., Begthel, H., Zandvliet, M. M. J. M., Doornaert, P., Raaijmakers, C. P. J., et al. (2023) · Med · doi:10.1016/j.medj.2023.04.003 · Cited by 118 · see citing works
Protein arginine methyltransferase 5 (PRMT5) dysregulation in cancer
Shailesh, H., Zakaria, Z. Z., Baiocchi, R. A., & Sif, S. (2018) · Oncotarget · doi:10.18632/oncotarget.26404 · Cited by 115 · see citing works
PRMT5 Modulates Splicing for Genome Integrity and Preserves Proteostasis of Hematopoietic Stem Cells
Tan, D. Q., Li, Y., Yang, C., Li, J., Tan, S. H., Chin, D. W. L., Nakamura‐Ishizu, A., Yang, H. H., & Suda, T. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.02.001 · Cited by 116 · see citing works
Oil for the cancer engine: The cross-talk between oncogenic signaling and polyamine metabolism
Arruabarrena-Aristorena, A., Zabala‐Letona, A., & Carracedo, A. (2018) · Science Advances · doi:10.1126/sciadv.aar2606 · Cited by 114 · see citing works
Discovery of AG-270, a First-in-Class Oral MAT2A Inhibitor for the Treatment of Tumors with Homozygous MTAP Deletion
Konteatis, Z. D., Travins, J. M., Größ, S., Marjon, K., Barnett, A., Mandley, E., Nicolay, B., Nagaraja, R., Chen, Y., Sun, Y., et al. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c01895 · Cited by 112 · see citing works
Self-citation
Protein Arginine Methyltransferase 5 (PRMT5) as an Anticancer Target and Its Inhibitor Discovery
Wang, Y., Hu, W., & Yuan, Y. (2018) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b00598 · Cited by 111 · see citing works
Biology of Melanoma
Ostrowski, S. M., & Fisher, D. E. (2020) · Hematology/Oncology Clinics of North America · doi:10.1016/j.hoc.2020.08.010 · Cited by 111 · see citing works
The translational challenges of precision oncology
Pich, O., Bailey, C., Watkins, T. B. K., Zaccaria, S., Jamal‐Hanjani, M., & Swanton, C. (2022) · Cancer Cell · doi:10.1016/j.ccell.2022.04.002 · Cited by 111 · see citing works
PRMT5 enhances tumorigenicity and glycolysis in pancreatic cancer via the FBW7/cMyc axis
Qin, Y., Hu, Q., Xu, J., Ji, S., Dai, W., Liu, W., Xu, W., Sun, Q., Zhang, Z., Ni, Q., et al. (2019) · Cell Communication and Signaling · doi:10.1186/s12964-019-0344-4 · Cited by 110 · see citing works
PRMT5 activates AKT via methylation to promote tumor metastasis
Huang, L., Zhang, X.-O., Rozen, E. J., Sun, X., Sallis, B., Verdejo‐Torres, O., Wigglesworth, K., Moon, D., Huang, T., Cavaretta, J. P., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-31645-1 · Cited by 109 · see citing works
PRMT5-dependent transcriptional repression of c-Myc target genes promotes gastric cancer progression
Liu, M., Yao, B., Gui, T., Guo, C., Wu, X., Li, J., Ma, L., Deng, Y., Xu, P., Wang, Y., et al. (2020) · Theranostics · doi:10.7150/thno.42047 · Cited by 108 · see citing works
The Promise for Histone Methyltransferase Inhibitors for Epigenetic Therapy in Clinical Oncology: A Narrative Review
Rugo, H. S., Jacobs, I. A., Sharma, S., Scappaticci, F. A., Paul, T. A., Jensen-Pergakes, K., & Malouf, G. G. (2020) · Advances in Therapy · doi:10.1007/s12325-020-01379-x · Cited by 108 · see citing works
PRMT1 loss sensitizes cells to PRMT5 inhibition
Gao, G., Zhang, L., Villarreal, O. D., He, W., Su, D., Bedford, E., Moh, P., Shen, J., Shi, X., Bedford, M. T., et al. (2019) · Nucleic Acids Research · doi:10.1093/nar/gkz200 · Cited by 107 · see citing works
Molecular analysis of urothelial cancer cell lines for modeling tumor biology and drug response
Nickerson, M., Witte, N., Im, K. M., Turan, S., Owens, C. R., Misner, K., Tsang, S. X., Cai, Z., Wu, S., Dean, M. C., et al. (2016) · Oncogene · doi:10.1038/onc.2016.172 · Cited by 106 · see citing works
Procaspase-3 Overexpression in Cancer: A Paradoxical Observation with Therapeutic Potential
Boudreau, M. W., Peh, J., & Hergenrother, P. J. (2019) · ACS Chemical Biology · doi:10.1021/acschembio.9b00338 · Cited by 104 · see citing works
Overview of Methionine Adenosyltransferase 2A (MAT2A) as an Anticancer Target: Structure, Function, and Inhibitors
Li, C., Gui, G., Zhang, L., Qin, A., Zhou, C., & Zha, X. (2022) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.2c00395 · Cited by 99 · see citing works
A synthetic lethal drug combination mimics glucose deprivation–induced cancer cell death in the presence of glucose
Joly, J. H., Delfarah, A., Phung, P. S., Parrish, S., & Graham, N. A. (2020) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)49891-7 · Cited by 97 · see citing works
Therapeutic Strategies for Targeting CDKN2A Loss in Melanoma
Kreuger, I. Z. M., Slieker, R. C., van Groningen, T., & van Doorn, R. (2022) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2022.07.016 · Cited by 97 · see citing works
The story of protein arginine methylation: characterization, regulation, and function
Peng, C., & Wong, C. C. L. (2017) · Expert Review of Proteomics · doi:10.1080/14789450.2017.1275573 · Cited by 96 · see citing works
Phase 1 Study of JNJ-64619178, a Protein Arginine Methyltransferase 5 Inhibitor, in Advanced Solid Tumors
Vieito, M., Moreno, V., Spreafico, A., Braña, I., Wang, J. S.-Z., Preis, M., Hernández‐Guerrero, T., Genta, S., Hansen, A. R., Doger, B., et al. (2023) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-23-0092 · Cited by 96 · see citing works
Self-citation
FGFR2 Extracellular Domain In-Frame Deletions Are Therapeutically Targetable Genomic Alterations That Function as Oncogenic Drivers in Cholangiocarcinoma
Cleary, J. M., Raghavan, S., Wu, Q., Li, Y. Y., Spurr, L. F., Gupta, H. V., Rubinson, D. A., Fetter, I. J., Hornick, J. L., Nowak, J. A., et al. (2021) · Cancer Discovery · doi:10.1158/2159-8290.cd-20-1669 · Cited by 95 · see citing works
Targeting Arginine Methyltransferase PRMT5 for Cancer Therapy: Updated Progress and Novel Strategies
Zheng, J., Li, B., Wu, Y., Wu, X., & Wang, Y. (2023) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.3c00250 · Cited by 94 · see citing works
Molecular basis for substrate recruitment to the PRMT5 methylosome
Mulvaney, K. M., Blomquist, C., Acharya, N., Li, R., Ranaghan, M. J., O’Keefe, M., Rodriguez, D. J., Young, M. J., Kesar, D., Pal, D., et al. (2021) · Molecular Cell · doi:10.1016/j.molcel.2021.07.019 · Cited by 93 · see citing works
Self-citation
SAM-Competitive PRMT5 Inhibitor PF-06939999 Demonstrates Antitumor Activity in Splicing Dysregulated NSCLC with Decreased Liability of Drug Resistance
Jensen-Pergakes, K., Tatlock, J., Maegley, K. A., McAlpine, I. J., McTigue, M., Xie, T., Dillon, C. P., Wang, Y., Yamazaki, S., Spiegel, N., et al. (2021) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-21-0620 · Cited by 92 · see citing works
PRMT5 in gene regulation and hematologic malignancies
Zhu, F., & Rui, L. (2019) · Genes & Diseases · doi:10.1016/j.gendis.2019.06.002 · Cited by 90 · see citing works
STC2 activates PRMT5 to induce radioresistance through DNA damage repair and ferroptosis pathways in esophageal squamous cell carcinoma
Jiang, K., Yin, X., Zhang, Q., Yin, J., Tang, Q., Xu, M., Wu, L., Shen, Y., Zhou, Z., Yu, H., et al. (2023) · Redox Biology · doi:10.1016/j.redox.2023.102626 · Cited by 90 · see citing works
Enzymatic Transition States and Drug Design
Schramm, V. L. (2018) · Chemical Reviews · doi:10.1021/acs.chemrev.8b00369 · Cited by 89 · see citing works
AMG 193, a Clinical Stage MTA-Cooperative PRMT5 Inhibitor, Drives Antitumor Activity Preclinically and in Patients with MTAP-Deleted Cancers
Belmontes, B., Slemmons, K. K., Su, C., Liu, S., Policheni, A. N., Moriguchi, J., Tan, H. L. E., Xie, F., Aiello, D. A., Yang, Y., et al. (2024) · Cancer Discovery · doi:10.1158/2159-8290.cd-24-0887 · Cited by 89 · see citing works
A synthetic lethal drug combination mimics glucose deprivation–induced cancer cell death in the presence of glucose
Joly, J. H., Delfarah, A., Phung, P. S., Parrish, S., & Graham, N. A. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.ra119.011471 · Cited by 88 · see citing works
Blocking methionine catabolism induces senescence and confers vulnerability to GSK3 inhibition in liver cancer
Li, F., Liu, P., Mi, W., Li, L., Anderson, N. M., Lesner, N. P., Burrows, M., Plesset, J. B., Majer, A. D., Wang, G., et al. (2024) · Nature Cancer · doi:10.1038/s43018-023-00671-3 · Cited by 88 · see citing works
Discovery of TNG908: A Selective, Brain Penetrant, MTA-Cooperative PRMT5 Inhibitor That Is Synthetically Lethal with MTAP -Deleted Cancers
Cottrell, K. M., Briggs, K. J., Whittington, D. A., Jahić, H., Ali, J. A., Davis, C. B., Gong, S., Gotur, D., Gu, L., McCarren, P. R., et al. (2024) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.4c00133 · Cited by 88 · see citing works
Metabolite sensing and signaling in cancer
Wang, Y.-P., Li, J., Qu, J., Yin, M., & Lei, Q. (2020) · Journal of Biological Chemistry · doi:10.1074/jbc.rev119.007624 · Cited by 84 · see citing works
MTAP deficiency creates an exploitable target for antifolate therapy in 9p21-loss cancers
Alhalabi, O., Chen, J., Zhang, Y., Lü, Y., Wang, Q., Ramachandran, S., Tidwell, R. S. S., Han, G., Yan, X., Meng, J., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-29397-z · Cited by 80 · see citing works
Loss of MAT2A compromises methionine metabolism and represents a vulnerability in H3K27M mutant glioma by modulating the epigenome
Golbourn, B. J., Halbert, M. E., Halligan, K. E., Varadharajan, S., Krug, B., Mbah, N. E., Kabir, N., Stanton, A.-C. J., Locke, A. L., Casillo, S. M., et al. (2022) · Nature Cancer · doi:10.1038/s43018-022-00348-3 · Cited by 80 · see citing works
Protein arginine methyltransferase 5: A novel therapeutic target for triple‐negative breast cancers
Vinet, M., Suresh, S., Maire, V., Monchecourt, C., Némati, F., Lesage, L., Pierre, F., Ye, M., Lescure, A., Brisson, A., et al. (2019) · Cancer Medicine · doi:10.1002/cam4.2114 · Cited by 79 · see citing works
Synthetic lethal strategies for the development of cancer therapeutics
Ngoi, N. Y. L., Gallo, D., Torrado, C., Nardo, M., Durocher, D., & Yap, T. A. (2024) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-024-00966-z · Cited by 78 · see citing works
ERG signaling in prostate cancer is driven through PRMT5-dependent methylation of the Androgen Receptor
Mounir, Z., Korn, J. M., Westerling, T., Lin, F., Kirby, C. A., Schirle, M., McAllister, G., Hoffman, G., Ramadan, N., Hartung, A., et al. (2016) · eLife · doi:10.7554/elife.13964 · Cited by 78 · see citing works
Self-citation
New Horizons of Synthetic Lethality in Cancer: Current Development and Future Perspectives
Previtali, V., Bagnolini, G., Ciamarone, A., Ferrandi, G., Rinaldi, F., Myers, S. H., Roberti, M., & Cavalli, A. (2024) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.4c00113 · Cited by 77 · see citing works
A Ubiquitination Cascade Regulating the Integrated Stress Response and Survival in Carcinomas
Cervia, L. D., Shibue, T., Borah, A. A., Gaeta, B., He, L., Leung, L., Li, N., Moyer, S. M., Shim, B. H., Dumont, N., et al. (2022) · Cancer Discovery · doi:10.1158/2159-8290.cd-22-1230 · Cited by 75 · see citing works
Targeting Histone Methylation in Cancer
McCabe, M. T., Mohammad, H. P., Barbash, O., & Kruger, R. G. (2017) · The Cancer Journal · doi:10.1097/ppo.0000000000000283 · Cited by 73 · see citing works

Abstract LB-017: Disordered methionine metabolism in MTAP/CDKN2A-deleted cancers leads to marked dependence on PRMT5
Mavrakis, K. J., McDonald, E. R., Schlabach, M. R., Billy, É., Hoffman, G. R., de Weck, A., Ruddy, D. A., Venkatesan, K., McAllister, G., deBeaumont, R. S., et al. (2016) · Cancer Research · doi:10.1158/1538-7445.am2016-lb-017 · Cited by 3 · see citing works
Self-citation
Methylthioadenosine phosphorylase deficiency in tumors: A compelling therapeutic target
Fan, N., Zhang, Y., & Zou, S. (2023) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2023.1173356 · Cited by 39 · see citing works
Abstract LB-307: MTAP deletions in cancer create vulnerability to a MAT2A/PRMT5/RIOK1 axis
Marks, K. M. (2016) · Cancer Research · doi:10.1158/1538-7445.am2016-lb-307
MTAP deletion confers enhanced dependency on the PRMT5 arginine methyltransferase in cancer cells
Kryukov, G. V., Wilson, F. H., Ruth, J. R., Paulk, J., Tsherniak, A., Marlow, S. E., Vazquez, F., Weir, B. A., Fitzgerald, M. E., Tanaka, M., et al. (2016) · Science · doi:10.1126/science.aad5214 · Cited by 688 · see citing works
544 DNA methylation: an epigenetic pathway to cancer and a promising target for anticancer therapy in breast cancer
Martinez-Galán, J., Delgado, J. R., Ávila, R. D. M., Torres, B. T., Núñez, M., Valdivia, J., Luque, R., Peñalver, J., Ríos-Arrabal, S., & de Almodóvar, M. R. (2010) · European Journal of Cancer Supplements · doi:10.1016/s1359-6349(10)72251-5 · Cited by 1 · see citing works

Authors: Mavrakis, K. J., McDonald, E. R., Schlabach, M. R., Billy, E., Hoffman, G. R., deWeck, A., Ruddy, D. A., Venkatesan, K., Yu, J., McAllister, G., Stump, M., deBeaumont, R., Ho, S., Yue, Y., Liu, Y., Yan-Neale, Y., Yang, G., Lin, F., Yin, H., Gao, H., Kipp, D. R., Zhao, S., McNamara, J. T., Sprague, E. R., Zheng, B., Lin, Y., Cho, Y. S., Gu, J., Crawford, K., Ciccone, D., Vitari, A. C., Lai, A., Capka, V., Hurov, K., Porter, J. A., Tallarico, J., Mickanin, C., Lees, E., Pagliarini, R., Keen, N., Schmelzle, T., Hofmann, F., Stegmeier, F., & Sellers, W. R.
Affiliations: Novartis Institutes for Biomedical Research, Cambridge, MA 02139, USA.
Novartis Institutes for Biomedical Research, Basel CH-4002, Switzerland.
Novartis Institutes for Biomedical Research, Emeryville, CA 94608, USA.
Novartis (China) (CN)
Novartis Institutes for BioMedical Research (CH)
Corresponding author: Mavrakis, Konstantinos J.
McDonald, E. Robert
Schlabach, Michael R.
Hoffman, Gregory R.
Schmelzle, Tobias
Hofmann, Francesco
Stegmeier, Frank
Sellers, William R.
ORCID: McDonald, E. Robert
Schlabach, Michael R.
Ruddy, David A.
Venkatesan, Kavitha
Yu, Jianjun
Ho, Samuel
Liu, Yue
Yin, Hong
Kipp, D. Randal
Zhao, Songping
McNamara, Joshua T.
Sprague, Elizabeth R.
Lin, Ying
Cho, Young Shin
Ciccone, David
Lai, Albert
Tallarico, John
Lees, Emma
Pagliarini, Raymond
Keen, Nicholas
Schmelzle, Tobias
Stegmeier, Frank
Sellers, William R.
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 2016-03-11
Volume: 351
Issue: 6278
Pages: 1208-1213
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.aad5944
OpenAlex: W2287840388
Cited by: 607
References: 29
Citations by year: 2026: 86 · 2025: 96 · 2024: 72 · 2023: 54 · 2022: 58 · 2021: 48 · 2020: 40 · 2019: 50 · 2018: 39 · 2017: 37 · 2016: 25
FWCI: 26.15
Type: journal article
Language: en
Open access: closed
Licence: www.sciencemag.org/about/science-licenses-journal-article-reuse (vor, 365 d)
Locations: Science (publishedVersion)
PubMed (publishedVersion)
Funders: Office of Science, Office of Basic Energy Sciences, U.S. Department of Energy (DE-AC02-06CH11357)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer-related gene regulation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA modifications and cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
Keywords: MTAP, CDKN2A, PRMT5, methylthioadenosine, methionine salvage pathway, methionine metabolism, cancer cell lines, PRMT5 inhibition, tumor suppressor loss, cancer metabolism, targeted cancer therapy
MeSH terms: Cell Survival, Deoxyadenosines, Humans, Methionine, Neoplasms, Protein-Arginine N-Methyltransferases, Purine-Nucleoside Phosphorylase, Thionucleosides, Gene Deletion, Cyclin-Dependent Kinase Inhibitor p16, RNA, Small Interfering, Cell Line, Tumor

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Disordered methionine metabolism in MTAP/CDKN2A-deleted cancers leads to dependence on PRMT5

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