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Library | Item Barcode | Call Number | Material Type | Item Category 1 | Status |
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Searching... | 30000010150731 | RC271.C5 D46 2006 | Open Access Book | Book | Searching... |
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Summary
Summary
Successful cancer chemotherapy relies heavily on the application of various deoxynucleoside analogs. Since the very beginning of modern cancer chemotherapy, a number of antimetabolites have been introduced into the clinic and subsequently applied widely for the treatment of many malignancies, both solid tumors and hematological disorders. In the latter diseases, cytarabine has been the mainstay of treatment of acute myeloid leukemia. Although many novel compounds were synthesized in the 1980s and 1990s, no real improvement was made. However, novel technology is now capable of elucidating the molecular basis of several inborn errors as well as some specific malignancies. This has enabled the synthesis of several deoxynucleoside analogs that could be applied for specific malignancies, such as pentostatin and subsequently chlorodeoxyadenosine (cladribine) for the treatment of hairy cell leukemia. Already in the early stage of deoxynucleoside analog development, it was recognized that several of these compounds were very effective in the treatment of various viral infections, such as for the treatment of herpes infections. This formed the basis initially for the design of azidothymidine and subsequently many other analogs, which are currently successfully used for the treatment of HIV infections. As a spin-off of these research lines, some compounds not eligible for development as antiviral agents appeared to be very potent anticancer agents. The classical example is gemcitabine, now one of the most widely applied deoxynucleoside analogs, used for the (combination) treatment of non-small cell lung cancer, pancreatic cancer, bladder cancer, and ovarian cancer.
Table of Contents
Preface | p. v |
Contributors | p. xi |
1 Nucleoside Transport Into Cells: Role of Nucleoside Transporters SLC28 and SLC29 in Cancer Chemotherapy | p. 1 |
2 The Role of Deoxycytidine Kinase in DNA Synthesis and Nucleoside Analog Activation | p. 29 |
3 Deoxynucleoside Kinases and Their Potential Role in Deoxynucleoside Cytotoxicity | p. 53 |
4 Nucleotidases and Nucleoside Analog Cytotoxicity | p. 81 |
5 Pumping Out Drugs: The Potential Impact of ABC Transporters on Resistance to Base, Nucleoside, and Nucleotide Analogs | p. 109 |
6 Cytosine Arabinoside: Metabolism, Mechanisms of Resistance, and Clinical Pharmacology | p. 119 |
7 Clofarabine: Mechanisms of Action, Pharmacology, and Clinical Investigations | p. 153 |
8 L-Nucleosides as Chemotherapeutic Agents | p. 173 |
9 Troxacitabine (Troxatyl): A Deoxycytidine Nucleoside Analog With Potent Antitumor Activity | p. 199 |
10 9-[Beta]-D-Arabinofuranosylguanine | p. 215 |
11 Gemcitabine: Mechanism of Action and Resistance | p. 225 |
12 Clinical Activity of Gemcitabine as a Single Agent and in Combination | p. 253 |
13 Nucleoside Radiosensitizers | p. 289 |
14 NONMEM Population Models of Cytosine Arabinoside and Fludarabine Phosphate in Pediatric Patients With Leukemia | p. 331 |
15 The cycloSal-Nucleotide Delivery System: Development of Chemical Trojan Horses as Antiviral Agents | p. 353 |
16 Purine and Pyrimidine-Based Analogs and Suicide Gene Therapy | p. 403 |
17 3[prime]-Deoxy-3[prime]-Fluorothymidine as a Tracer of Proliferation in Positron Emission Tomography | p. 441 |
Index | p. 463 |