Summary
Tumor-specific screening of investigational anticancer drugs is a new approach to cytotoxic drug screening. A tumor-specific drug screening model has been designed using established human neuroblastoma cell lines. In vitro drug sensitivity was studied using a modification of the human tumor stem cell assay. Eleven cell lines were tested initially for colony formation in soft agar. Four cell lines formed only small cell clusters, while three cell lines formed colonies at a very low rate. The four remaining lines formed colonies with satisfactory efficiency. These cell lines were exposed to three concentrations each of cis-platinum, vincristine, doxorubicin, L-phenylalanine mustard, and ethidium chloride and suspended in soft agar. Colony formation was tabulated and sensitivities determined for each cell line. A heterogeneous pattern of in vitro sensitivity was observed. Limitations and pitfalls as well as potential advantages of using such a tumor-specific drug screening system are discussed.
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Venditti JM: Evolution and current status of the antitumor screening program of the National Cancer Institute (NCI), USA, 3rd EORTC-NCI New Drug Meeting, abs #30, 1981
Salmon SE, Von Hoff DD: In vitro evaluation of anticancer drugs with the human tumor stem cell assay. Seminars in Oncol 8:377–385, 1981
Seeger RC, Rayner SA, Banerjee A, Chung H, Lang WE, Neu HB, Benedict WF: Morphology, growth, chromosome pattern and fibrinolytic activity of two new human neuroblastoma cell lines. Cancer Res 37:1364–1371, 1977
Seeger RC, Zeltzer PM, Rayner SA: Onco-neural antigen: A new neural differentiation antigen expressed by neuroblastoma, oat cell carcinoma, ‘Wilms’ tumor, and sarcoma cells. J Immunol 122:1548–1555, 1979
Schlesinger HR, Rocke L, Jamison R, Hunmeler K: Neuronal properties of neuroectodermal tumors in vitro. Cancer Res 41:2573–2575, 1981
Biedler J, Helson L, Spengeer BA: Morphology and growth, tumorigenicity and cytogenetics of neuroblastoma cells in continuous culture. Cancer Res 33:2643–2652, 1973
Tumilowicz JJ, Nichols WW, Chalon JJ, Greene AE: Definition of a continuous human cell line derived from neuroblastoma. Cancer Res 30:2110–2118, 1970
Hamburger AW, Salmon SE: Primary bioassay of human tumor stem cells. Science 197:461–463, 1977
Chu MY, Takeuchi T, Yeskey KS, Bogaars H, Calabresi P: Tumor cell heterogeneity in human lung carcinoma LX-1. Proc Am Assoc Cancer Res 20:151, 1979
Martin DS, Fugmann RA, Stolfi RL, Hayworth PE: Solid tumor animal model therapeutically predictive for human breast cancer. Cancer Chemother Rep 5:89–109, 1975
Bogden AE, Kelton DE, Cobb WR, Esber HJ: A rapid screening method for testing chemotherapeutic agents against human tumor xenografts. In Houchens DP, Ovejera AA (eds) Proceedings of the Symposium on the Use of Athymic (Nude) Mice in Cancer Research. Gustav Fischer, New York, 1978, pp 231–250
Bellet RE, Danna V, Mastrangelo MJ, Berd D: Evaluation of a ‘nude’ mouse-human tumor panel as a predictive secondary screen for cancer chemotherapeutic agents. J Natl Cancer Inst 63:1185–1188, 1979
Moon TE: Quantitative and statistical analysis of the association between in vitro and in vivo studies. In: Salmon SE (ed) Cloning of Human Tumor Stem Cells. Alan R Liss Inc, New York, 1980, pp 209–221
Von Hoff DD, Casper S, Bradley E, Sandbach J, Jones D, Makuch R: Association between human tumor colonyforming assay results and response of an individual patient's tumor to chemotherapy. Am J Med 70:1027–1041, 1981
Salmon S: In vitro phase II trials with the human tumor clonogenic assay. 13th Intl Cong Chemother 22:43–48, 1983
Von Hoff DD, Lathan B, Clark GM, Sandbach JF, Cowan JD: The human tumor cloning system as a predictor of phase II activity of bisantrene. 13th Intl Cong Chemother 213:5–7, 1983
Von Hoff DD, Coltman CA Jr, Forseth B: Activity of mitoxantrone in a human tumor cloning system. Cancer Res 41:1853–1855, 1981
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Supported by an Institutional grant from the American Cancer Society No. IN-116G.
Supported by Robert J. and Helen C. Kleberg Foundation.
Dr. Zeltzer is a Junior Faculty Clinical Fellow 542 of the American Cancer Society.
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Sarosdy, M.F., Schneider, S.L., Forseth, B.J. et al. In vitro Chemosensitivity testing of human neuroblastoma cell lines in soft agar: A tumor — specific drug screening model. Invest New Drugs 4, 135–139 (1986). https://doi.org/10.1007/BF00194592
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DOI: https://doi.org/10.1007/BF00194592