Anti-Neoplastics Pcol

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Aldehyde Dehydrogenase

Back 1

Detoxifies Cyclophosposphamide precurser (not to acrolein)

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Cupport Transporters/OCT2

Back 2

Responsible for Uptake of Pt compounds. Found in cancers and prox tub cells

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GSH

Back 3

Responsible for detox of Pt compounds (prox tub cells lack it)

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Mesna

Back 4

Cytoprotectant for Cyclophosphamide for bladder, prevents cystitis

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Amifostine

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Cytoprotectant for Pt compounds, free sulfhydryl neturalizes Pt in kidney

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Nucleotide Excision Repair

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Enzy responsible for repairing DNA damage

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Translesion synthase

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Enzyme responsible for skipping over DNA damage in synthesis

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FPGS and FPGH (folate polyglucomate sythase/ hydrolase

Back 8

Enzmes responsible for activation of MTX and inactivation of MTX in cell

Front 9

DHFR (Dihydrofolate Reductase)

Back 9

Enzyme, converts DHF=> THF to be used as cofactor for TYMS, inhibt by MTX

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TYMS (Thymidylate Synthase)

Back 10

Enzyme, uses THF to convert dUMP=> dTMP, Inhib. by MTX, 5-FU, Capecitabine

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Leucovorin

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Cytoprotective for MTX, Potentiator for 5-FU/Capecitabine

Front 12

Dihydropyrimidine Dehydrogenase (DPD)

Back 12

Detoxifies 5-FU/capecitabine, POLYMORPH = deficiency

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Xantine Oxidase

Back 13

Detoxifies 6-MP, inihbited by allopurinol and febuxustat (DDI)

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Thiopurine Methyltranserase (TPMT)

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Detoxifies 6-MP/6-TG, POLYMORPH = Toxicity

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DNA Methyltransferase

Back 15

Upreg in cancer, methylates C residues = gene silencing, inhibit by 5-Azacytidine and decitabine

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Ribonucleotide Reductase

Back 16

Enzyme that synthesizes dNTP from NTPs, inhibited by Hydroxyurea

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Topo I

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ssDNA break, Inhibted by campothecans

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Topo II

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dsDNA break, ATP dep, inhibted by antracyclines and etop and teniposide

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UGT 1A1

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UGT enzyme, glucuronidates irinotecan to inactive SN-38 gluc (bile exc). POLYMORPH *28/*28 = deficiency

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Dexrazoxane

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Cytoprotectant, chelates low mw fe= decreases ox species in cardiac myocytes for DOXORUBICIN

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L-Asparginase

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Enzyme given to decrease levels of L-Asparagine available for Tumor scavenge = decreased tumor growth

Front 22

CYP 2D6

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CYP responsible for conversion of Tamoxifen => Endoxifen (more active/cytotoxic), POLYMORPH = decreased efficacy

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Aromatase

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Enzyme responsible for conversion of Adrenal products to estradiol and estrone. Tx inhibits in BR+ Breast cancer

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CTLA-4 Receptor

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Receptor on T-Cells, translocates, displaces CD28 and binds w/ B7 on APC and results in turning off of T-Cells bound to APC. Inhibited by Ipilumumab

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PAP (Prostate Acid Phosphatase)

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Surface marker expressed by Prostate cancer, Sipuleucel-T programs T cells against PAP

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CD20

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Receptor found on B-Cells, Bound by Rituxumab, Tositumomab, Ibritumomab

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EGFR

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Epidermal Growth Factor (ERBB1)

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HER2

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Human Epidermal growth factor Receptor 2 (ERBB2)

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PI3K/AKT

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Activation pathway of Tyr Kinase receptors

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Ras

Back 30

Adapter molecule responsible for phosphorylation/activation of of MAPK pathway, k-ras mutation =constiuently active Tyr Kinase (HER2) PHAMACOGENOMIC TEST: K-ras mutations

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BCR-ABL

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Philidel. chromosome, fusion of BCR-ABL gene =fusion protein w/ constiuently active Tyr Kinase (BCR-ABL Kinase). Dx: CML, PHARMGENETIC: Mutation prone

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T315I

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Mutation of BCR-ABL = altered AA's in binding pocket = less H-bonding of Tyr kinase inhibitors. Only tx = Ponatinib PHARMACOGENETIC TEST: