Gene therapy has expanded rapidly over the last decade. The number of clinical trials reported by 2001 included 532 protocols and 3436 patients. Phase I trials predominate with 359 trials of 1774 patients versus Phase II (57 trials with 507 patients) and Phase III (3 trials of 251 patients). The disease overwhelmingly targeted by gene therapy is cancer: involving 331 trials with 2361 patients. Despite the somewhat disappointing results of clinical trials to date, gene therapy offers tremendous promise for the future of cancer therapy. The area of gene therapy is vast, and both malignant and nonmalignant cells can be targeted. Suicide Gene Therapy: Methods and Reviews covers gene therapy that targets malignant cells in a treatment that has become known as "suicide gene therapy. " Basically, this approach uses the transduction of cancer cells with a gene for a foreign enzyme that, when expressed, is able to activate a nontoxic prodrug into a highly cytotoxic drug able to kill the cancer cell population. This is a major area in cancer gene therapy-in 2001 this technique was represented by 52 clinical protocols with a total of 567 patients. Additional trials used multiple gene therapy protocols that also involved suicide gene therapy (83 with 497 patients), indicating that the interest in this area is considerable. Suicide Gene Therapy: Methods and Reviews aims to cover comprehensively, both in theoretical and practical terms, the rapidly evolving area of suicide gene therapy for cancer.
Introduction to the Background, Principles, and State of the Art in Suicide Gene TherapyIon Niculescu-Duvaz and Caroline J. SpringerIntroduction to Vectors for Suicide Gene TherapyCaroline J. SpringerConstruction of VNP20009: A Novel, Genetically Stable Antibiotic-Sensitive Strain of Tumor-Targeting Salmonella for Parenteral Administration in HumansKenneth Brooks Low, Martina Ittensohn, Xiang Luo, Li-Mou Zheng, Ivan King, John M. Pawelek, and David BermudesNonreplicating DNA Viral Vectors for Suicide Gene Therapy: The Adenoviral VectorsMasato Yamamoto and David T. CurielReplication-Selective Oncolytic AdenovirusesGunnel Hallden, Stephen H. Thorne, Jingping Yang, and David H. KirnRetroviral Vectors for Suicide Gene TherapyColin PorterNonviral LiposomesAndrew D. MillerPeptide- and Polymer-Based Gene Delivery VehiclesRichard Brokx and Jean GariepyDesign of Prodrugs for Suicide Gene TherapyDan Niculescu-Duvaz, Ion Niculescu-Duvaz, and Caroline J. SpringerCytochrome P450-Based Gene Therapies for CancerE. Antonio Chiocca and David J. WaxmanTumor Sensitization to Purine Analogs by E. coli PNPKimberly V. Curlee, William B. Parker, and Eric J. SorscherEnzyme-Prodrug Systems: Carboxylesterase/CPT-11Mary K. Danks and Philip M. PotterEnzyme-Prodrug Systems: Thymidine Phosphorylase/5'-Deoxy-5-FluorouridineAlexandre Evrard, Joseph Ciccolini, Pierre Cuq, and Jean-Paul CanoMethods to Improve Efficacy in Suicide Gene Therapy Approaches: Targeting Prodrug-Activating Enzymes Carboxypeptidase G2 and Nitroreductase to Different Subcellular CompartmentsSilke Schepelmann, Robert Spooner, Frank Friedlos, and Richard MaraisExtracellular b-Glucuronidase for Gene-Directed Enzyme-Prodrug TherapySabine BrusselbachEnhancementof Suicide Gene Prodrug Activation by Random MutagenesisJean-Emmanuel Kurtz and Margaret E. BlackCombination Suicide Gene TherapyWolfgang Uckert, Brian Salmons, Christian Beltinger, Walter H. Gunzburg, and Thomas KammertoensImmune Response to Suicide Gene TherapyShigeki Kuriyama, Hirohisa Tsujinoue, and Hitoshi YoshijiTargeting Cancer With Gene Therapy Using Hypoxia as a StimulusGabi U. Dachs, Olga Greco, and Gillian M. TozerRadiation-Activated Antitumor VectorsSimon D. Scott and Brian MarplesIn Vitro and In Vivo Models for the Evaluation of GDEPT: Quantifying Bystander Killing in Cell Cultures and TumorsWilliam R. Wilson, Susan M. Pullen, Alison Hogg, Stephen M. Hobbs, Frederik B. Pruijn, and Kevin O. HicksSuicide Gene Therapy in Liver TumorsLong R. Jiao, Roman Havlik, Joanna Nicholls, Steen Lindkaer Jensen, and Nagy A. HabibClinical Trials With GDEPT: Cytosine Deaminase and 5-FluorocytosineNicola L. Brown and Nicholas R. LemoineThe Nitroreductase/CB1954 Enzyme-Prodrug SystemNicola K. Green, David J. Kerr, Vivien Mautner, Peter A. Harris, and Peter F. SearleSide Effects of Suicide Gene TherapyMarjolijn M. van der Eb, Bertie de Leeuw, Alex J. van der Eb, and Rob C. HoebenAntibody-Directed Enzyme-Prodrug TherapyR. Barbara Pedley, Surinder K. Sharma, Robert E. Hawkins, and Kerry A. ChesterBioreductive Prodrugs for Cancer TherapyBeatrice Seddon, Lloyd R. Kelland, and Paul WorkmanIndex