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809 results

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Page 1
MTAP as an emerging biomarker in thoracic malignancies.
Brune MM, Savic Prince S, Vlajnic T, Chijioke O, Roma L, König D, Bubendorf L. Brune MM, et al. Lung Cancer. 2024 Nov;197:107963. doi: 10.1016/j.lungcan.2024.107963. Epub 2024 Sep 29. Lung Cancer. 2024. PMID: 39357262 Free article. Review.
Besides, MTAP loss, which has been reported in 13% of NSCLC, is becoming an emerging predictive biomarker in two different scenarios in NSCLC and other cancer types: 1) MTAP loss seems to negatively predict the response to immune checkpoint inhibitor (ICI) treatment …
Besides, MTAP loss, which has been reported in 13% of NSCLC, is becoming an emerging predictive biomarker in two different scenarios …
MRTX1719 Is an MTA-Cooperative PRMT5 Inhibitor That Exhibits Synthetic Lethality in Preclinical Models and Patients with MTAP-Deleted Cancer.
Engstrom LD, Aranda R, Waters L, Moya K, Bowcut V, Vegar L, Trinh D, Hebbert A, Smith CR, Kulyk S, Lawson JD, He L, Hover LD, Fernandez-Banet J, Hallin J, Vanderpool D, Briere DM, Blaj A, Marx MA, Rodon J, Offin M, Arbour KC, Johnson ML, Kwiatkowski DJ, Jänne PA, Haddox CL, Papadopoulos KP, Henry JT, Leventakos K, Christensen JG, Shazer R, Olson P. Engstrom LD, et al. Cancer Discov. 2023 Nov 1;13(11):2412-2431. doi: 10.1158/2159-8290.CD-23-0669. Cancer Discov. 2023. PMID: 37552839 Free PMC article. Clinical Trial.
MRTX1719 selectively inhibited PRMT5 in the presence of MTA, which is elevated in MTAP del cancers, and inhibited PRMT5-dependent activity and cell viability with >70-fold selecti-vity in HCT116 MTAP del compared with HCT116 MTAP wild-type (WT) cells. MRTX …
MRTX1719 selectively inhibited PRMT5 in the presence of MTA, which is elevated in MTAP del cancers, and inhibited PRMT5-dependent act …
MTAP deletion confers enhanced dependency on the PRMT5 arginine methyltransferase in cancer cells.
Kryukov GV, Wilson FH, Ruth JR, Paulk J, Tsherniak A, Marlow SE, Vazquez F, Weir BA, Fitzgerald ME, Tanaka M, Bielski CM, Scott JM, Dennis C, Cowley GS, Boehm JS, Root DE, Golub TR, Clish CB, Bradner JE, Hahn WC, Garraway LA. Kryukov GV, et al. Science. 2016 Mar 11;351(6278):1214-8. doi: 10.1126/science.aad5214. Epub 2016 Feb 11. Science. 2016. PMID: 26912360 Free PMC article.
MTAP is frequently lost due to its proximity to the commonly deleted tumor suppressor gene, CDKN2A. We observed increased intracellular concentrations of methylthioadenosine (MTA, the metabolite cleaved by MTAP) in cells harboring MTAP deletions. Furthermore, …
MTAP is frequently lost due to its proximity to the commonly deleted tumor suppressor gene, CDKN2A. We observed increased intracellul …
MTAP loss: a possible therapeutic approach for glioblastoma.
Patro CPK, Biswas N, Pingle SC, Lin F, Anekoji M, Jones LD, Kesari S, Wang F, Ashili S. Patro CPK, et al. J Transl Med. 2022 Dec 26;20(1):620. doi: 10.1186/s12967-022-03823-8. J Transl Med. 2022. PMID: 36572880 Free PMC article. Review.
In this article, we review the loss of the 5'-methylthioadenosine phosphorylase (MTAP) gene as a potential therapeutic approach for treating glioblastoma. MTAP encodes a metabolic enzyme required for the metabolism of polyamines and purines leading to DNA synthesis. …
In this article, we review the loss of the 5'-methylthioadenosine phosphorylase (MTAP) gene as a potential therapeutic approach for t …
Disordered methionine metabolism in MTAP/CDKN2A-deleted cancers leads to dependence on PRMT5.
Mavrakis KJ, McDonald ER 3rd, Schlabach MR, Billy E, Hoffman GR, deWeck A, Ruddy DA, 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 DR, Zhao S, McNamara JT, Sprague ER, Zheng B, Lin Y, Cho YS, Gu J, Crawford K, Ciccone D, Vitari AC, Lai A, Capka V, Hurov K, Porter JA, Tallarico J, Mickanin C, Lees E, Pagliarini R, Keen N, Schmelzle T, Hofmann F, Stegmeier F, Sellers WR. Mavrakis KJ, et al. Science. 2016 Mar 11;351(6278):1208-13. doi: 10.1126/science.aad5944. Epub 2016 Feb 11. Science. 2016. PMID: 26912361
5-Methylthioadenosine phosphorylase (MTAP) is a key enzyme in the methionine salvage pathway. The MTAP gene is frequently deleted in human cancers because of its chromosomal proximity to the tumor suppressor gene CDKN2A. ...Deletion of MTAP in MTAP-pro …
5-Methylthioadenosine phosphorylase (MTAP) is a key enzyme in the methionine salvage pathway. The MTAP gene is frequently dele …
Genomic landscape of non-small-cell lung cancer with methylthioadenosine phosphorylase (MTAP) deficiency.
Ashok Kumar P, Graziano SL, Danziger N, Pavlick D, Severson EA, Ramkissoon SH, Huang RSP, Decker B, Ross JS. Ashok Kumar P, et al. Cancer Med. 2023 Jan;12(2):1157-1166. doi: 10.1002/cam4.4971. Epub 2022 Jun 23. Cancer Med. 2023. PMID: 35747993 Free PMC article.
Statistically significant differences in mitogenic driver alterations included more KRAS G12C mutations in MTAP-intact versus MTAP-lost (12% vs. 10%, p = 0.0003) and fewer EGFR short variant mutations in MTAP-intact versus MTAP-lost NSCLC (10% vs. 13%, …
Statistically significant differences in mitogenic driver alterations included more KRAS G12C mutations in MTAP-intact versus MTAP …
MAT2A Inhibition Blocks the Growth of MTAP-Deleted Cancer Cells by Reducing PRMT5-Dependent mRNA Splicing and Inducing DNA Damage.
Kalev P, Hyer ML, Gross S, Konteatis Z, Chen CC, Fletcher M, Lein M, Aguado-Fraile E, Frank V, Barnett A, Mandley E, Goldford J, Chen Y, Sellers K, Hayes S, Lizotte K, Quang P, Tuncay Y, Clasquin M, Peters R, Weier J, Simone E, Murtie J, Liu W, Nagaraja R, Dang L, Sui Z, Biller SA, Travins J, Marks KM, Marjon K. Kalev P, et al. Cancer Cell. 2021 Feb 8;39(2):209-224.e11. doi: 10.1016/j.ccell.2020.12.010. Epub 2021 Jan 14. Cancer Cell. 2021. PMID: 33450196 Free article.
The methylthioadenosine phosphorylase (MTAP) gene is located adjacent to the cyclin-dependent kinase inhibitor 2A (CDKN2A) tumor-suppressor gene and is co-deleted with CDKN2A in approximately 15% of all cancers. ...The metabolic enzyme methionine adenosyltransferase 2alpha …
The methylthioadenosine phosphorylase (MTAP) gene is located adjacent to the cyclin-dependent kinase inhibitor 2A (CDKN2A) tumor-supp …
MTAP Deletions in Cancer Create Vulnerability to Targeting of the MAT2A/PRMT5/RIOK1 Axis.
Marjon K, Cameron MJ, Quang P, Clasquin MF, Mandley E, Kunii K, McVay M, Choe S, Kernytsky A, Gross S, Konteatis Z, Murtie J, Blake ML, Travins J, Dorsch M, Biller SA, Marks KM. Marjon K, et al. Cell Rep. 2016 Apr 19;15(3):574-587. doi: 10.1016/j.celrep.2016.03.043. Epub 2016 Apr 7. Cell Rep. 2016. PMID: 27068473 Free article.
MTAP-deleted cells have reduced PRMT5 methylation activity and increased sensitivity to PRMT5 depletion. ...Thus, the unique biochemical features of PRMT5 create an axis of targets vulnerable in CDKN2A/MTAP-deleted cancers....
MTAP-deleted cells have reduced PRMT5 methylation activity and increased sensitivity to PRMT5 depletion. ...Thus, the unique biochemi …
MTAP Deficiency-Induced Metabolic Reprogramming Creates a Vulnerability to Cotargeting De Novo Purine Synthesis and Glycolysis in Pancreatic Cancer.
Hu Q, Qin Y, Ji S, Shi X, Dai W, Fan G, Li S, Xu W, Liu W, Liu M, Zhang Z, Ye Z, Zhou Z, Yang J, Zhuo Q, Yu X, Li M, Xu X. Hu Q, et al. Cancer Res. 2021 Oct 1;81(19):4964-4980. doi: 10.1158/0008-5472.CAN-20-0414. Epub 2021 Aug 12. Cancer Res. 2021. PMID: 34385182 Free article.
In vitro experiments demonstrated that the glycolysis inhibitor 2-deoxy-d-glucose (2-DG) and the de novo purine synthesis inhibitor l-alanosine synergized to kill MTAP-deficient pancreatic cancer cells. Collectively, these results reveal that MTAP deficiency drives …
In vitro experiments demonstrated that the glycolysis inhibitor 2-deoxy-d-glucose (2-DG) and the de novo purine synthesis inhibitor l-alanos …
MTAP deficiency creates an exploitable target for antifolate therapy in 9p21-loss cancers.
Alhalabi O, Chen J, Zhang Y, Lu Y, Wang Q, Ramachandran S, Tidwell RS, Han G, Yan X, Meng J, Wang R, Hoang AG, Wang WL, Song J, Lopez L, Andreev-Drakhlin A, Siefker-Radtke A, Zhang X, Benedict WF, Shah AY, Wang J, Msaouel P, Zhang M, Guo CC, Czerniak B, Behrens C, Soto L, Papadimitrakopoulou V, Lewis J, Rinsurongkawong W, Rinsurongkawong V, Lee J, Roth J, Swisher S, Wistuba I, Heymach J, Wang J, Campbell MT, Efstathiou E, Titus M, Logothetis CJ, Ho TH, Zhang J, Wang L, Gao J. Alhalabi O, et al. Nat Commun. 2022 Apr 4;13(1):1797. doi: 10.1038/s41467-022-29397-z. Nat Commun. 2022. PMID: 35379845 Free PMC article. Clinical Trial.
Here we report our single arm phase II trial (NCT02693717) that assesses pemetrexed in MTAP(def) urothelial carcinoma (UC) with the primary endpoint of overall response rate (ORR). Three of 7 enrolled MTAP(def) patients show response to pemetrexed (ORR 43%). Further …
Here we report our single arm phase II trial (NCT02693717) that assesses pemetrexed in MTAP(def) urothelial carcinoma (UC) with the p …
809 results