Principles of Chemotherapy - Experimental Oncology Graduate Study

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Nucleoside analogs: Membrane transportproteins and drug resistance• Drug-specific transporters such as hENT1 (human equilibrative nucleosidetransporter 1) are responsible for the uptake of important anticancer nucleosideanalogs, such as gemcitabine.• Down-regulation of hENT1 might thus represent a mechanism of resistance tosuch drugs.G hENT1 G dCK GP GPPPCN-II1Courtesy of Dr. J. Mackey.28
Nucleoside analog responsiveness and hENT1• hENT1 immunohistochemistryon 21 consecutive patientstreated with gemcitabine forpalliation ofadvanced/recurrent pancreaticadenocarcinoma.1009080PERCENT SURVIVING70605040Kaplan-Meier Survival by hENT1 Intensityfrom Gemcitabine Initiation (n=21)p = 0.014negpos30201000 6 12 18 24 30MONTHSJ. Spratlin, R. Sangha, D. Glubrecht, L. Dabbagh, J.Young, C. Dumontet, C. Cass, R. Lai, J. Mackey.Clin Cancer Res. 2004;10:6956-61.Overall patient survival from initiationof gemcitabine therapy in pancreaticcancer29
Page 1 and 2: ONCOLOGY 520CHEMOTHERAPYLecturer: D
Page 3 and 4: Combination CT• Improvements in C
Page 5 and 6: Therapeutic Index, contd.• Such d
Page 7 and 8: Relationship between remission and
Page 9 and 10: Classes of anticancer drugs• “C
Page 11 and 12: a. Nitrogen mustards• Bifunctiona
Page 13 and 14: Melphalan (LMelphalan(L-phenylalani
Page 15 and 16: . Chloroethyl nitrosoureas• The 2
Page 17 and 18: 2. AntimetabolitesDrugs that resemb
Page 19 and 20: Antimetabolites, contd.Cytosine ara
Page 21 and 22: Natural products, contd.Actinomycin
Page 23 and 24: Natural products, contd.VP-16 and V
Page 25 and 26: 4. “Platinating” agents: Cispla
Page 27: 1. Transport• Mutation/altered ex
Page 31 and 32: 2. Glutathione and associated enzym
Page 33 and 34: 4. Tolerance to DNA damage• In ma
Page 35 and 36: 5. Drug-specific mechanisms• Ctx:
Page 37 and 38: Cell-cycle phase specificity of CT
Page 39 and 40: [2] Use of high-dose CT through ove
Page 41 and 42: Bone marrow transplantation and gen
Page 43 and 44: Gleevec (imatinib mesylate), former
Page 45 and 46: Hypoxic-cell cell cytotoxins: Tirap

Principles of Chemotherapy - Experimental Oncology Graduate Study

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