Predictive Drug Testing on Human Tumor Cells

Predictive drug testing on human tumor cells in order to define the appropriate chemotherapy will remain imperative as long as the anticancer agents available are few in number and show only limited activity. The advantages of an effective test would lie in obviating the need for testing antineoplastic agents on large cohorts of patients for assessment of drug activity (phase II studies) and in allowing determination of optimal use of anticancer agents (phase III trials). Such an in vitro test could help to better define dose and schedule of drugs preclinically. The additive value of individual drugs could be determined on tumor cells in vitro in order to define the best combination chemotherapy in vivo. Test-directed therapy would avoid unnecessary drug-related morbidity in patients with refractory tumors. Chemotherapy treatment would be more than justified even with side effects if palliation or even prolonged survival could be anticipated as a result. The benefits of predictive drug testing on human tumor cells would extend beyond improvement of individual patient treatment if the testing helped to identify new active agents. This spectrum of benefits to the entire field of oncology pro vides tremendous motivation for the development of such testing. Although a number of chemosensitivity tests have been proposed since the advent of modern anticancer chemotherapy, interest has been renewed by the possibility of cloning human tumor cells on agar plates, with a view to testing drug activity on cells with high pro liferation capacity.

Inhalt
Clonogenic Assays for Solid Tumors.- In Vitro Growth of Human Malignancies in a Cloning Assay.- Development and Applications of a Human Tumor Colony Assay for Chemosensitivity Testing.- A Replenishable Soft Agar Colony Assay for Human Tumor Sensitivity Testing.- Analysis of Malignant Effusions by Cellular Composition, Proliferation Kinetics, and In Vitro Clonogenicity.- Direct Cloning of Human Ovarian Cancer in Soft Agar: Clinical Limitations and Pharmacologic Applications.- Technical Problems with Soft Agar Colony Formation Assays for In Vitro Chemotherapy Sensitivity Testing of Human Solid Tumors: Mayo Clinic Experience.- Cloning of Human Tumor Cells in Methylcellulose-Containing Medium.- The Effect of Chemotherapy on Human Bone Sarcomas: A Clinical and Experimental Study.- Predictive Tests for Hematological Malignancies.- Experimental Approaches to Outcome Prediction in Acute Myeloblastic Leukemia.- Experimental Approaches to Drug Testing and Clonogenic Growth: Results in Multiple Myeloma and Acute Myelogenous Leukemia.- In Vitro Assessment of Drug Sensitivity in Acute Nonlymphocytic Leukemia.- Short-Term In Vitro Sensitivity Testing in Acute Leukemia.- Non-Clonogenic Assays for Drug Testing.- Development of a Nucleotide Precursor Incorporation Assay for Testing Drug Sensitivity of Human Tumors.- Predictive Relevance for Clinical Outcome of In Vitro Sensitivity Evaluated Through Antimetabolic Assay.- Biochemical Short-Term Predictive Assay: Results of Correlative Trials in Comparison to Other Assays.- In Vitro Chemosensitivity Assay Based on the Concept of Total Tumor Cell Kill.- Evaluation of In Vitro Results.- Predictive Tests and Infrequent Events in Cancer Chemotherapy.- Pharmacologic Pitfalls in the Human Tumor Clonogenic Assay.- Heterogeneity and Variability ofTest Results as Limiting Factors for Predictive Assays.- Interlaboratory Comparison of In Vitro Cloning of Fresh Human Tumor Cells from Malignant Effusions.- Pharmacology, Phase II Studies and New Drug Development.- Evaluation of Schedule Dependency of Anticancer Drugs in the Human Tumor Clonogenic Assay.- In Vitro Effect of Interferon-a on Human Granulocyte/Macrophage Progenitor Cells and Human Clonogenic Tumor Cells..- Effect of Leukocyte Interferons on Cell Proliferation of Human Tumors in Vitro.- Drug Combination Testing with In Vitro Clonal Cultures.- Neutralization of cis-Dichlorodiammineplatinum II and Nitrogen Mustard by Thiols.- Usefulness of the Human Tumor Colony Forming Assay for New Drug Development.- In Vitro Characterization of New Antiestrogens in Human Mammary Tumor Cells.- Modulation of Tumor Growth by Non-Chemotherapeutic Intervention.- Growth Factor Enhancement of the In Vitro Stem Cell Assay.- Improving Techniques for Clonogenic Assays.- Relationship of Steroid Hormone Receptors to the Cloning of Fresh Breast Cancer Tissues.