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Chemotherapy is a type of cancer treatment that uses one or more anti-cancer drugs as part of a standardized chemotherapy regimen. Chemotherapy may be given with a curative intent, or it may aim to prolong life or to reduce symptoms. Chemotherapy is one of the major categories of the medical discipline specifically devoted to pharmacotherapy for cancer, which is called medical oncology.
Fluorouracil (5-FU), sold under the brand name Adrucil among others, is a chemotherapy medication used to treat cancer. By injection into a vein it is used for colon cancer, esophageal cancer, stomach cancer, pancreatic cancer, breast cancer, and cervical cancer. As a cream it is used for actinic keratosis, basal cell carcinoma, and skin warts.
An antimetabolite is a chemical that inhibits the use of a metabolite, which is another chemical that is part of normal metabolism. Such substances are often similar in structure to the metabolite that they interfere with, such as the antifolates that interfere with the use of folic acid; thus, competitive inhibition can occur, and the presence of antimetabolites can have toxic effects on cells, such as halting cell growth and cell division, so these compounds are used as chemotherapy for cancer.
The era of cancer chemotherapy began in the 1940s with the first use of nitrogen mustards and folic acid antagonist drugs. The targeted therapy revolution has arrived, but many of the principles and limitations of chemotherapy discovered by the early researchers still apply.
HAT Medium is a selection medium for mammalian cell culture, which relies on the combination of aminopterin, a drug that acts as a powerful folate metabolism inhibitor by inhibiting dihydrofolate reductase, with hypoxanthine and thymidine which are intermediates in DNA synthesis. The trick is that aminopterin blocks DNA de novo synthesis, which is absolutely required for cell division to proceed, but hypoxanthine and thymidine provide cells with the raw material to evade the blockage, provided that they have the right enzymes, which means having functioning copies of the genes that encode them.
{{Drugbox | verifiedrevid = 464379925 | IUPAC_name = N-[(5-{methyl[ methyl]amino}-2-thienyl)carbonyl]-L-glutamic acid | image = Raltitrexed.svg | image2 = Raltitrexed ball-and-stick.png | tradename = | Drugs.com = Micromedex Detailed Consumer Information | pregnancy_AU = | pregnancy_US = | pregnancy_category = | legal_AU = | legal_UK = POM | legal_US = Not available | legal_status = | routes_of_administration = Intravenous | bioavailability = | protein_bound = | metabolism = | elimination_half-life = | excretion = | IUPHAR_ligand = 7403 | CAS_number_Ref = | CAS_number = 112887-68-0 | ATC_prefix = L01 | ATC_suffix = BA03 | ATC_supplemental = | PubChem = 104758 | DrugBank_Ref = | DrugBank = DB00293 | ChemSpiderID_Ref = | ChemSpiderID = 94568 | UNII_Ref = | UNII = FCB9EGG971 | KEGG_Ref = | KEGG = D01064 | ChEMBL_Ref = | ChEMBL = 225071 | PDB_ligand = D16 | C=21 | H=22 | N=4 | O=6 | S=1 | smiles = O=C(c3sc cc3)N[C@H](C O)CCC(=O)O | StdInChI_Ref = | StdInChI = 1S/C21H22N4O6S/c1-11-22-14-4-3-12(9-13 19 23-11)10-25(2)17-7-6-16(32-17)20(29)24-15(21 31)5-8-18(26)27/h3-4,6-7,9,15H,5,8,10H2,1-2H3,(H,24,29)(H,26,27)(H,30,31)(H,22,23,28)/t15-/m0/s1 | StdInChIKey_Ref = | StdInChIKey = IVTVGDXNLFLDRM-HNNXBMFYSA-N }}
Thymidylate synthase (TS) is an enzyme that catalyzes the conversion of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP). Thymidine is one of the nucleotides in DNA. With inhibition of TS, an imbalance of deoxynucleotides and increased levels of dUMP arise. Both cause DNA damage.
5,10-Methylenetetrahydrofolate (N5,N10-Methylenetetrahydrofolate; 5,10-CH2-THF) is cofactor in several biochemical reactions. It exists in nature as the diastereoisomer [6R]-5,10-methylene-THF.
In enzymology, a thymidylate synthase (FAD) (EC 2.1.1.148) is an enzyme that catalyzes the chemical reaction
Antifolates are a class of antimetabolite medications that antagonise (that is, block) the actions of folic acid (vitamin B9). Folic acid's primary function in the body is as a cofactor to various methyltransferases involved in serine, methionine, thymidine and purine biosynthesis. Consequently, antifolates inhibit cell division, DNA/RNA synthesis and repair and protein synthesis. Some such as proguanil, pyrimethamine and trimethoprim selectively inhibit folate's actions in microbial organisms such as bacteria, protozoa and fungi. The majority of antifolates work by inhibiting dihydrofolate reductase (DHFR).
Carmofur (INN) or HCFU (1-hexylcarbamoyl-5-fluorouracil) is a pyrimidine analogue used as an antineoplastic agent. It is a derivative of fluorouracil, being a lypophilic-masked analog of 5-FU that can be administered orally.
OSI-7904 is a noncompetitive liposomal thymidylate synthase inhibitor. OSI-7904 is a benzoquinazoline folate analog with antineoplastic activity. As a thymidylate synthase inhibitor, OSI-7904 noncompetitively binds to thymidylate synthase, resulting in inhibition of thymine nucleotide synthesis and DNA replication.
Thymectacin is an anticancer prodrug of brivudine monophosphate. It developed by New Biotics and it has entered in phase I clinical trials for colon cancer.
Wafik El-Deiry is an American physician and cancer researcher who is the Associate Dean for Oncologic Sciences at the Warren Alpert Medical School, Brown University and the Director of the Joint Program in Cancer Biology at Brown University and its affiliated hospitals. He was previously Deputy Director of Translational Research at Fox Chase Cancer Center, where he was also co-Leader of the Molecular Therapeutics Program.
Thymidylate kinase catalyzes the phosphorylation of thymidine 5'-monophosphate (dTMP) to form thymidine 5'-diphosphate (dTDP) in the presence of ATP and magnesium:
Trifluridine/tipiracil, sold under the brand name Lonsurf, is a fixed-dose combination medication that is used as a third- or fourth-line treatment of metastatic colorectal cancer or gastric cancer, after chemotherapy and targeted therapeutics have failed. It is a combination of two active pharmaceutical ingredients: trifluridine, a nucleoside analog, and tipiracil, a thymidine phosphorylase inhibitor. Tipiracil prevents rapid metabolism of trifluridine, increasing the bioavailability of trifluridine.
Antineoplastic resistance, often used interchangeably with chemotherapy resistance, is the resistance of neoplastic (cancerous) cells, or the ability of cancer cells to survive and grow despite anti-cancer therapies. In some cases, cancers can evolve resistance to multiple drugs, called multiple drug resistance.
ONX-0801 is an experimental drug that has been developed to target ovarian cancer. It is a folate receptor alpha mediated thymidylate synthase inhibitor.
Professor Kenneth Reginald Harrap (1931-2017) was a British oncological biochemist.
Fluorodeoxyuridylate, also known as FdUMP, 5-Fluoro-2'-deoxyuridylate, or 5-Fluoro-2'-deoxyuridine 5'-monophosphate sodium salt, is a molecule formed in vivo from 5-fluorouracil or 5-fluorodeoxyuridin.
References
- ↑ Jackman AL, Calvert AH (November 1995). "Folate-based thymidylate synthase inhibitors as anticancer drugs". Annals of Oncology. 6 (9): 871–81. doi: 10.1093/oxfordjournals.annonc.a059353 . PMID 8624289.
- ↑ Ackland SP, Clarke SJ, Beale P, Peters GJ (December 2006). "Thymidylate synthase inhibitors". Update on Cancer Therapeutics. 1 (4): 403–427. doi:10.1016/j.uct.2006.09.001.
- ↑ "Thymidylate synthase inhibitors as anticancer agents: from bench to bedside" . Retrieved 2009-01-28.
- ↑ Liu Y, Wu W, Hong W, Sun X, Wu J, Huang Q (April 2014). "Raltitrexed-based chemotherapy for advanced colorectal cancer". Clinics and Research in Hepatology and Gastroenterology. 38 (2): 219–25. doi:10.1016/j.clinre.2013.11.006. PMID 24388340.
- ↑ Papamichael D (1999). "The use of thymidylate synthase inhibitors in the treatment of advanced colorectal cancer: current status". The Oncologist. 4 (6): 478–87. doi:10.1634/theoncologist.4-6-478. PMID 10631692.
- ↑ Gibbs DD, Theti DS, Wood N, Green M, Raynaud F, Valenti M, Forster MD, Mitchell F, Bavetsias V, Henderson E, Jackman AL (December 2005). "BGC 945, a novel tumor-selective thymidylate synthase inhibitor targeted to alpha-folate receptor-overexpressing tumors". Cancer Research. 65 (24): 11721–8. doi: 10.1158/0008-5472.CAN-05-2034 . PMID 16357184.
- ↑ Ricart AD, Berlin JD, Papadopoulos KP, Syed S, Drolet DW, Quaratino-Baker C, Horan J, Chick J, Vermeulen W, Tolcher AW, Rowinsky EK, Rothenberg ML (December 2008). "Phase I, pharmacokinetic and biological correlative study of OSI-7904L, a novel liposomal thymidylate synthase inhibitor, and cisplatin in patients with solid tumors". Clinical Cancer Research. 14 (23): 7947–55. doi: 10.1158/1078-0432.CCR-08-0864 . PMID 19047127.
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