Over the last several decades, the introduction of new chemotherapeutic drugs and drug combinations has resulted in increased long­ term remission rates in several important tumor types. These include childhood leukemia, adult leukemias and lymphomas, as well as testicular and trophoblastic tumors. The addition of high-dose chemotherapy with growth factor and hemopoietic stem cell support has increased clinical remission rates even further. For the majority of patients with some of the more common malignancies, however, palliation (rather than cure) is still the most realistic goal of chemotherapy for metastatic disease. The failure of chemotherapy to cure metastatic cancer is commonly referred to among clinicians as "drug resistance". This phenomenon can, however, often be viewed as the survival of malignant cells that resulted from a failure to deliver an effective drug dose to the (cellular) target because of anyone of or combination of a multitude of individual factors. Clinically, this treatment failure is often viewed as the rapid occurrence of resistance at the single cell level. However, in experimental systems, stable drug resistance is usually relatively slow to emerge.

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List of contributors. Preface. 1. Tumor physiology and resistance to chemotherapy: repopulation and drug penetration; A.J. Davis, I.F. Tannock. 2. The role of membrane transporters in cellular resistance to anticancer nucleoside drugs; M.L. Clarke, et al. 3. MDR and MRP gene families as cellular determinant factors for resistance to clinical anticancer agents; L. Deng, et al. 4. The glutathione system in alkylator resistance; D. Hamilton, et al. 5. The role of signal transduction pathways in drug and radiation resistance; S. Grant, et al. 6. Mechanisms of repair of interstrand crosslinks in DNA; R.J. Legerski, C. Richie. 7. DNA repair in resistance to bifunctional alkylating and platinating agents; D. Murray. 8. Leukemic cell insensitivity to cyclophosphamide and other oxazaphosphorines mediated by aldehyde dehydrogenase(s); N.E. Sládek. 9. Mechanisms of resistance against cyclophosphamide and ifosfamide: can they be overcome without sacrificing selectivity? S.M. Ludeman, M.P. Gamcsik. 10. Cellular mechanisms of cyclophosphamide resistance: model studies in human medulloblastoma cell lines; H.S. Friedman, et al. 11. Model studies of cyclophosphamide resistance in human myeloid leukemia; B.S. Andersson, D. Murray. 12. Mechanisms of drug resistance in AML; M. Andreeff, M. Konopleva. 13. Biochemical and molecular mechanisms of cisplatin resistance; Z.H. Siddik. 14. Modification of radiosensitivity following chemotherapy exposure: potential implications for combined-modality therapy; R.A. Britten. 15. Clinical pharmacology of melphalan and itsimplications for clinical resistance to anticancer agents; R.B. Jones. 16. Pharmacological considerations of primary alkylators; J.S. McCune, J.T. Slattery. 17. Genomic approaches to clinical drug resistance; S. Damaraju, et al. Index.