Nucleoside Transport into Cells: The Role of Nucleoside Transporters SLC28 and SLC29 in Cancer Chemotherapyn Marcal Pastor-Anglada and F. Javier Casadon n The Role of Deoxycytidine Kinase in DNA Synthesis and Nucleoside Analog Activationn Maria Staub and Staffan Erikssonn n Deoxynucleoside Kinases and Their Potential Role in Deoxynucleoside Cytotoxicityn Birgitte Munch-Petersen and Jure Piskurn n Nucleotidases and Nucleoside Analog Cytotoxicityn Sally Anne Hunsucker, Beverly S. Mitchell, and Jozef Spychalan n Pumping Out Drugs: The Potential Impact of ABC Transporters on Resistance to Base, Nucleoside, and Nucleotide Analogsn Piet Borst and Peter Wielingan n Cytosine Arabinoside: Metabolism, Mechanisms, of Resistance, and Clinical Pharmacologyn Isabelle Hubeek, G. J. L. Kaspers, G Ossenkoppele, and G. J. Petersn n Clofarabine: Mechanisms of Action, Pharmacology, and Clinical Investigationn Varsha Gandhi and William Plunkettn n L-Nucleosides as Chemotherapeutic Agentsn Giuseppe Gumina, Youhoon Chong, and Chung K. Chun n Troxacitabine: A Deoxycytidine Nucleoside Analogue With Potent Antitumor Activityn Henriette Gourdeau and Jacques Jolivetn n 9-b-D-arabinofuranosylguaninen Sophie Curbon n Gemcitabine: Mechanism of Action and Resistancen A. M. Bergman and G.J. Petersn n Clinical Activity of Gemcitabine as a Single Agent and in Combinationn J. R. Kroep, GJ Peters, and RA Nagourneyn n Nucleoside Radiosensitizersn Donna S. Shewach and Theodore S. Lawrencen n NONMEM Population Models of Cytosine Arabinoside and Flubaradine Phosphate in Pediatric Patients with Leukemia n Vassilios I. Avramisn n The cycloSal-Nucleotide Delivery System: Development of Chemical Trojan Horses as Antiviral Agentsn Chris Meier, Jan Balzarini, and Astrid Meerbachn n Purine and Pyrimidine Based Analogs and Suicide GeneTherapyn Zoran Gojkovicn n 3'-deoxy-3'- Fluorothymidine as a Tracer if Proliferation in Positron Emission Tomography
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.
Deoxynucleoside Analogs in Cancer Therapy expertly summarizes the current status of development and application of deoxynucleoside analogs. Authoritative up-to-date reviews are presented by scientists well known in their specific areas and all contributions include valuable sound advice on structure and topics. This volume focuses on novel aspects of deoxynucleoside analogs in the clinical context, as well as on unexpected targets of these compounds, such as their specific activity against cell cycle-dependent kinases or oncogenes. The information presented can be used to design rational combinations aimed at inhibiting various cellular signaling pathways, or combining inhibition of various targets. Deoxynucleoside Analogs in Cancer Therapy has been designed specifically to facilitate such an interaction between various fields.