Molecular Mechanisms of Resistance to Antifolates a Review
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| Proper noun | Antifolate resistance | ||||||||
| Description | Since the 1940s, antifolates have played a pivotal role in drug handling of cancerous, microbial, parasitic and chronic inflammatory diseases. The molecular footing of the anti-proliferative action of antifolates relies on inhibition of key enzymes in folate metabolism, which results in disruption of purine and thymidylate biosynthesis, inhibition of Deoxyribonucleic acid replication and prison cell decease. The anti-inflammatory properties of antifolate take been most strongly related to its power to block the release of pro-inflammatory cytokines such as tumour necrosis gene (TNF)-blastoff or interleukin (IL)-1beta. Cells may develop resistance to an antifolate drug by virtue of impaired drug transport into cells, augmented drug export, impaired activation of antifolates through polyglutamylation, augmented hydrolysis of antifolate polyglutamates, increased expression and mutation of target enzymes, and the augmentation of cellular tetrahydrofolate-cofactor pools in cells. | ||||||||
| Class | Human Diseases; Drug resistance: antineoplastic | ||||||||
| Pathway map |
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| Reference | PMID:22921318 | ||||||||
| Authors | Gonen N, Assaraf YG | ||||||||
| Title | Antifolates in cancer therapy: structure, activity and mechanisms of drug resistance. | ||||||||
| Periodical | Drug Resist Updat 15:183-210 (2012) | ||||||||
| Reference | PMID:17333344 | ||||||||
| Authors | Assaraf YG | ||||||||
| Title | Molecular basis of antifolate resistance. | ||||||||
| Journal | Cancer Metastasis Rev 26:153-81 (2007) | ||||||||
| Reference | PMID:26920997 | ||||||||
| Authors | Municio C, Soler Palacios B, Estrada-Capetillo L, Benguria A, Dopazo A, Garcia-Lorenzo E, Fernandez-Arroyo S, Joven J, Miranda-Carus ME, Gonzalez-Alvaro I, Puig-Kroger A | ||||||||
| Championship | Methotrexate selectively targets man proinflammatory macrophages through a thymidylate synthase/p53 centrality. | ||||||||
| Journal | Ann Rheum Dis 75:2157-2165 (2016) | ||||||||
| Reference | PMID:24732946 | ||||||||
| Authors | Wilson PM, Danenberg PV, Johnston PG, Lenz HJ, Ladner RD | ||||||||
| Title | Continuing the test of fourth dimension: targeting thymidylate biosynthesis in cancer therapy. | ||||||||
| Journal | Nat Rev Clin Oncol 11:282-98 (2014) | ||||||||
| Reference | PMID:18297517 | ||||||||
| Authors | Fotoohi AK, Albertioni F | ||||||||
| Title | Mechanisms of antifolate resistance and methotrexate efficacy in leukemia cells. | ||||||||
| Journal | Leuk Lymphoma 49:410-26 (2008) | ||||||||
| Reference | PMID:17203006 | ||||||||
| Authors | van der Heijden JW, Dijkmans BA, Scheper RJ, Jansen One thousand | ||||||||
| Title | Drug Insight: resistance to methotrexate and other disease-modifying antirheumatic drugs--from bench to bedside. | ||||||||
| Journal | Nat Clin Pract Rheumatol 3:26-34 (2007) | ||||||||
| Reference | PMID:17092765 | ||||||||
| Authors | Assaraf YG | ||||||||
| Title | The role of multidrug resistance efflux transporters in antifolate resistance and folate homeostasis. | ||||||||
| Journal | Drug Resist Updat ix:227-46 (2006) | ||||||||
| Reference | |||||||||
| Authors | Mauritz R. | ||||||||
| Championship | Determinants of antifolate and v-fluorouracil efficacy | ||||||||
| Periodical | Biochemistry | ||||||||
| Reference | |||||||||
| Authors | del-Campo LS, Montenegro MF, Saez-Ayala M, Fernandez-Perez MP, Cabezas-Herrera J, Rodriquez-Lopez JN. | ||||||||
| Championship | Cellular and molecular mechanisms of methotrexate resistance in melanoma | ||||||||
| Journal | Intech | ||||||||
| Reference | PMID:16380836 | ||||||||
| Authors | Walling J | ||||||||
| Title | From methotrexate to pemetrexed and across. A review of the pharmacodynamic and clinical properties of antifolates. | ||||||||
| Journal | Invest New Drugs 24:37-77 (2006) | ||||||||
| Reference | PMID:22954694 | ||||||||
| Authors | Desmoulin SK, Hou Z, Gangjee A, Matherly LH | ||||||||
| Title | The human proton-coupled folate transporter: Biology and therapeutic applications to cancer. | ||||||||
| Journal | Cancer Biol Ther 13:1355-73 (2012) | ||||||||
| Reference | PMID:16491071 | ||||||||
| Authors | Cheok MH, Evans WE | ||||||||
| Championship | Acute lymphoblastic leukaemia: a model for the pharmacogenomics of cancer therapy. | ||||||||
| Periodical | Nat Rev Cancer 6:117-29 (2006) | ||||||||
| Reference | PMID:23987246 | ||||||||
| Authors | van der Heijden JW, Assaraf YG, Gerards AH, Oerlemans R, Lems WF, Scheper RJ, Dijkmans BA, Jansen 1000 | ||||||||
| Title | Methotrexate analogues display enhanced inhibition of TNF-alpha production in whole blood from RA patients. | ||||||||
| Journal | Scand J Rheumatol 43:nine-16 (2014) | ||||||||
| Reference | PMID:8793930 | ||||||||
| Authors | Gorlick R, Goker E, Trippett T, Waltham M, Banerjee D, Bertino JR | ||||||||
| Title | Intrinsic and acquired resistance to methotrexate in astute leukemia. | ||||||||
| Journal | N Engl J Med 335:1041-8 (1996) | ||||||||
| Reference | PMID:15117425 | ||||||||
| Authors | Adjei AA | ||||||||
| Championship | Pharmacology and machinery of action of pemetrexed. | ||||||||
| Periodical | Clin Lung Cancer 5 Suppl 2:S51-5 (2004) | ||||||||
| Reference | PMID:14576850 | ||||||||
| Authors | Zhao R, Goldman ID | ||||||||
| Title | Resistance to antifolates. | ||||||||
| Journal | Oncogene 22:7431-57 (2003) | ||||||||
| Reference | PMID:21317831 | ||||||||
| Authors | Mikkelsen TS, Thorn CF, Yang JJ, Ulrich CM, French D, Zaza G, Dunnenberger HM, Marsh Due south, McLeod HL, Giacomini K, Becker ML, Gaedigk R, Leeder JS, Kager L, Relling MV, Evans W, Klein TE, Altman RB | ||||||||
| Title | PharmGKB summary: methotrexate pathway. | ||||||||
| Journal | Pharmacogenet Genomics 21:679-86 (2011) | ||||||||
| Reference | PMID:23897011 | ||||||||
| Authors | Blits M, Jansen G, Assaraf YG, van de Wiel MA, Lems WF, Nurmohamed MT, van Schaardenburg D, Voskuyl AE, Wolbink GJ, Vosslamber Southward, Verweij CL | ||||||||
| Title | Methotrexate normalizes upward-regulated folate pathway genes in rheumatoid arthritis. | ||||||||
| Periodical | Arthritis Rheum 65:2791-802 (2013) | ||||||||
| Reference | PMID:11509639 | ||||||||
| Authors | Majumdar South, Aggarwal BB | ||||||||
| Title | Methotrexate suppresses NF-kappaB activation through inhibition of IkappaBalpha phosphorylation and degradation. | ||||||||
| Journal | J Immunol 167:2911-20 (2001) | ||||||||
| Related pathway |
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Source: https://www.genome.jp/dbget-bin/www_bget?ko01523
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