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Cancer Pharmacogenomics
Cancer pharmacogenomics is the study of how variances in the genome influences an individual’s response to different Treatment of cancer, cancer drug treatments. It is a subset of the broader field of pharmacogenomics, which is the area of study aimed at understanding how genetic variants influence drug efficacy and toxicity. Cancer is a genetic disease where changes to genes can cause cells to grow and divide out of control. Each cancer can have a unique combination of Mutation, genetic mutations, and even cells within the same tumour may have different genetic changes. In clinical settings, it has commonly been observed that the same types and doses of treatment can result in substantial differences in efficacy and toxicity across patients. Thus, the application of pharmacogenomics within the field of cancer can offer key advantages for personalizing cancer therapy, minimizing treatment toxicity, and maximizing treatment efficacy. This can include choosing drugs that target spec ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Tyrosine Kinase Inhibitor
A tyrosine kinase inhibitor (TKI) is a pharmaceutical drug that inhibits tyrosine kinases. Tyrosine kinases are enzymes responsible for the activation of many proteins by signal transduction cascades. The proteins are activated by adding a phosphate group to the protein (phosphorylation), a step that TKIs inhibit. TKIs are typically used as anticancer drugs. For example, they have substantially improved outcomes in chronic myelogenous leukemia. They have also been used to treat other diseases, such as idiopathic pulmonary fibrosis. They are also called tyrphostins, the short name for "tyrosine phosphorylation inhibitor", originally coined in a 1988 publication, which was the first description of compounds inhibiting the catalytic activity of the epidermal growth factor receptor (EGFR). The 1988 study was the first demonstration of a systematic search and discovery of small-molecular-weight inhibitors of tyrosine phosphorylation, which do not inhibit protein kinases that phosphor ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Bilirubin
Bilirubin (BR) (adopted from German, originally bili—bile—plus ruber—red—from Latin) is a red-orange compound that occurs in the normcomponent of the straw-yellow color in urine. Another breakdown product, stercobilin, causes the brown color of feces. Although bilirubin is usually found in animals rather than plants, at least one plant species, '' Strelitzia nicolai'', is known to contain the pigment. Structure Bilirubin consists of an open-chain tetrapyrrole. It is formed by oxidative cleavage of a porphyrin in heme, which affords biliverdin. Biliverdin is reduced to bilirubin. After conjugation with glucuronic acid, bilirubin is water-soluble and can be excreted. Bilirubin is structurally similar to the pigment phycobilin used by certain algae to capture light energy, and to the pigment phytochrome used by plants to sense light. All of these contain an open chain of four pyrrolic rings. Like these other pigments, some of the double-bonds in bilirubin isomer ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Glucuronidation
Glucuronidation is often involved in drug metabolism of substances such as drugs, pollutants, bilirubin, androgens, estrogens, mineralocorticoids, glucocorticoids, fatty acid derivatives, retinoids, and bile acids. These linkages involve glycosidic bonds. Mechanism Glucuronidation consists of transfer of the glucuronic acid component of uridine diphosphate glucuronic acid to a substrate by any of several types of UDP-glucuronosyltransferase. UDP-glucuronic acid (glucuronic acid linked via a glycosidic bond to uridine diphosphate) is an intermediate in the process and is formed in the liver. One example is the N-glucuronidation of an aromatic amine, 4-aminobiphenyl, by UGT1A4 or UGT1A9 from human, rat, or mouse liver. : The substances resulting from glucuronidation are known as glucuronides (or glucuronosides) and are typically much more water- soluble than the non-glucuronic acid-containing substances from which they were originally synthesised. The human body uses g ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
UGT1A1
UDP-glucuronosyltransferase 1-1, also known as UGT-1A, is an enzyme that in humans is encoded by the ''UGT1A1'' gene. UGT-1A is a uridine diphosphate glucuronosyltransferase (UDP-glucuronosyltransferase, UDPGT or UGT), an enzyme of the glucuronidation pathway that transforms small lipophilic (fat-soluble) molecules, such as steroids, bilirubin, hormones, and drugs, into water-soluble, excretable metabolites. Gene The UGT1A1 gene is part of a complex locus that encodes several UDP-glucuronosyltransferases. The locus includes thirteen unique alternative first exons followed by four common exons. Four of the alternate first exons are considered pseudogenes. Each of the remaining nine 5' exons may be spliced to the four common exons, resulting in nine proteins with different N-termini and identical C-termini. Each first exon encodes the substrate binding site, and is regulated by its own promoter. Over 100 genetic variants within the UGT1A1 gene have been described, some of wh ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Neurotoxicity
Neurotoxicity is a form of toxicity in which a biological, chemical, or physical agent produces an adverse effect on the structure or function of the central and/or peripheral nervous system. It occurs when exposure to a substance – specifically, a neurotoxin or neurotoxicant– alters the normal activity of the nervous system in such a way as to cause permanent or reversible damage to nervous tissue. This can eventually disrupt or even kill neurons, which are cells that transmit and process signals in the brain and other parts of the nervous system. Neurotoxicity can result from organ transplants, radiation treatment, certain drug therapies, recreational drug use, exposure to heavy metals, bites from certain species of venomous snakes, pesticides, certain industrial cleaning solvents, fuels and certain naturally occurring substances. Symptoms may appear immediately after exposure or be delayed. They may include limb weakness or numbness, loss of memory, vision, and/or inte ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
5-Fluorouracil
Fluorouracil (5-FU, 5-fluorouracil), sold under the brand name Adrucil among others, is a cytotoxic chemotherapy medication used to treat cancer. By intravenous injection it is used for treatment of colorectal cancer, oesophageal 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. Side effects of use by injection are common. They may include inflammation of the mouth, loss of appetite, low blood cell counts, hair loss, and inflammation of the skin. When used as a cream, irritation at the site of application usually occurs. Use of either form in pregnancy may harm the fetus. Fluorouracil is in the antimetabolite and pyrimidine analog families of medications. How it works is not entirely clear, but it is believed to involve blocking the action of thymidylate synthase and thus stopping the production of DNA. Fluorouracil was patented in 1956 and came into medical u ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Dihydropyrimidine Dehydrogenase (NADP+)
In enzymology, a dihydropyrimidine dehydrogenase (NADP+) () is an enzyme that catalyzes the chemical reaction :5,6-dihydrouracil + NADP+ \rightleftharpoons uracil + NADPH + H+ Thus, the two substrates of this enzyme are 5,6-dihydrouracil and NADP+, whereas its 3 products are uracil, NADPH, and H+. In humans the enzyme is encoded by the ''DPYD'' gene. It is the initial and rate-limiting step in pyrimidine catabolism. It catalyzes the reduction of uracil and thymine. It is also involved in the degradation of the chemotherapeutic drugs 5-fluorouracil and tegafur. It also participates in beta-alanine metabolism and pantothenate and coa biosynthesis. Terminology The systematic name of this enzyme class is 5,6-dihydrouracil:NADP+ 5-oxidoreductase. Other names in common use include: * dihydrothymine dehydrogenase *dihydrouracil dehydrogenase (NADP+) *4,5-dihydrothymine: oxidoreductase *DPD *DHPDH *dehydrogenase, dihydrouracil (nicotinamide adenine dinucleotide, phosphate) ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Antimetabolite
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 in chemotherapy for cancer. Function Cancer treatment Antimetabolites can be used in cancer treatment, as they interfere with DNA production and therefore cell division and tumor growth. Because cancer cells spend more time dividing than other cells, inhibiting cell division harms tumor cells more than other cells. Antimetabolite drugs are commonly used to treat leukemia, cancers of the breast, ovary, and the gastrointestinal tract, as well as other types of cancers. In the Anatomical Therapeutic Chemical Class ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Thiopurine Methyltransferase
Thiopurine methyltransferase or thiopurine S-methyltransferase (TPMT) is an enzyme that in humans is encoded by the ''TPMT'' gene. A pseudogene for this locus is located on chromosome 18q. Function Thiopurine methyltransferase methylates thiopurine compounds. The methyl donor is S-adenosyl-L-methionine, which is converted to S-adenosyl-L-homocysteine. This enzyme metabolizes thiopurine drugs via S-adenosyl-L-methionine as the S-methyl donor and S-adenosyl-L-homocysteine as a byproduct. Clinical significance Thiopurine drugs such as 6-mercaptopurine are used as chemotherapeutic agents and immunosuppressive drugs. Genetic polymorphisms that affect this enzyme's activity are correlated with variations in sensitivity and toxicity to such drugs. About 1/300 individual is deficient for the enzyme. Pharmacology TPMT is best known for its role in the metabolism of the thiopurine drugs such as azathioprine, 6-mercaptopurine and 6-thioguanine. TPMT catalyzes the ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Pharmacodynamic Genes And Drugs
Pharmacodynamics (PD) is the study of the biochemical and physiologic effects of drugs (especially pharmaceutical drugs). The effects can include those manifested within animals (including humans), microorganisms, or combinations of organisms (for example, infection). Pharmacodynamics and pharmacokinetics are the main branches of pharmacology, being itself a topic of biology interested in the study of the interactions of both endogenous and exogenous chemical substances with living organisms. In particular, pharmacodynamics is the study of how a drug affects an organism, whereas pharmacokinetics is the study of how the organism affects the drug. Both together influence dosing, benefit, and adverse effects. Pharmacodynamics is sometimes abbreviated as PD and pharmacokinetics as PK, especially in combined reference (for example, when speaking of PK/PD models). Pharmacodynamics places particular emphasis on dose–response relationships, that is, the relationships between drug conc ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Ponatinib
Ponatinib, sold under the brand name Iclusig, is a medication used for the treatment of chronic myeloid leukemia and Philadelphia chromosome–positive (Ph+) acute lymphoblastic leukemia. It was developed by Ariad Pharmaceuticals. It is a multi-targeted tyrosine-kinase inhibitor. Some forms of chronic myeloid leukemia, those that have the T315I mutation, are resistant to current therapies such as imatinib. Ponatinib has been designed to be effective against these types of tumors. Ponatinib was approved for medical use in the United States in December 2012, and in the European Union in July 2013. Medical uses Ponatinib in indicated for the treatment of adults with Philadelphia chromosome-positive acute lymphoblastic leukemia and chronic myeloid leukemia. In March 2024, the FDA expanded the indication to include the treatment, with chemotherapy, for adults with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia. Adverse effects The US Food and D ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
