Summary
We have applied an in vitro soft-agar tumor-colony assay (which is now applicable to a variety of human cancers) to measurement of in vitro sensitivity to drugs and prediction of clinical response to cancer chemotherapy. The assay predicts drug resistance with 96% accuracy and sensitivity (in heavily pretreated patients) with 62% accuracy. On a pharmacokinetic basis the zone in vitro sensitivity for any given drug was only 5%–10% of the clinical concentration-time product (Cxt) achievable. This suggests that intratumoral drug concentrations in vivo may be lower than those in the plasma, and/or that > 2 log kills of tumor stem cells (not measurable in the assay) are required for clinical response. Serial in vitro studies showed that acquisition of drug resistance is a common clinical phenomenon which can be directly detected and quantitated in vitro.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Bruce WR, Meeker BE, Valeriote FA (1966) Comparison of the sensitivity of normal hematopoietic and transplanted lymphoma colony-forming cells to chemotherapeutic agents administered in vivo. J Natl Cancer Inst 37:233–245
Fisher RA (1960) The design of experiments, 7th edn. Hafner, New York
Hamburger AW, Kim MB, Salmon SE (1979) The nature of cells generating human myeloma colonies in vitro. J Cell Physiol 98:371–376
Hamburger A, Salmon SE (1977) Primary bioassay of human myeloma stem cells. J Clin Invest 60:846–854
Hamburger AW, Salmon SE (1977) Primary bioassay of human tumor stem cells. Science 197:461–463
Hamburger AW, Salmon SE, Kim MB, Trent SM, Soehnlen BJ, Alberts DS, Schmidt HJ (1978) Direct cloning of human ovarian carcinoma cells in agar. Cancer Res 38:3438–3443
Jones SE, Hamburger AW, Kim MB, Salmon SE (1979) Development of a bioassay for putative human lymphoma stem cells. Blood 53:294–303
Meyskens FL, Salmon SE (1979) Inhibition of human melanoma colony formation by retinoids. Cancer Res 40:4055–4057
Ogawa M, Bergsagel DE, McCulloch EA (1973) Chemotherapy of mouse myeloma: Quantitative cell culture predictive of response in vivo. Blood 41:7–15
Park CH, Bergsagel DE, McCulloch EA (1971) Mouse myeloma tumor stem cells: A primary cell culture assay. J Natl Cancer Inst 46:411–422
Salmon SE (1980) Morphologic studies of tumor colonies. In: Salmon SE (ed) Cloning of human tumor stem cells. Alan Liss, New York
Salmon SE, Hamburger AW (1978) Immunoproliferation and cancer: A common macrophage-derived promoter substance. Lancet 1:1289–1290
Salmon SE, Hamburger AW, Soehnlen BJ, Durie BGM, Alberts DS, Moon TC (1978) Quantitation of differential sensitivities of human tumor stem cells to anticancer drugs. N Engl J Med 298:1321–1327
Steel CG (1973) Cytokinetics of neoplasia. In: Holland JF, Frei E III (eds) Cancer medicine. Lea and Febiger, Philadelphia
Von Hoff DD, Johnson GE (1979) Secretion of tumor markers in the human tumor stem cell system. Proc Am Assoc Cancer Res 20: (abstr 206)
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1980 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Salmon, S.E. et al. (1980). Clinical Correlations of Drug Sensitivity in the Human Tumor Stem Cell Assay. In: Mathé, G., Muggia, F.M. (eds) Cancer Chemo- and Immunopharmacology. Recent Results in Cancer Research, vol 74. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-81488-4_36
Download citation
DOI: https://doi.org/10.1007/978-3-642-81488-4_36
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-81490-7
Online ISBN: 978-3-642-81488-4
eBook Packages: Springer Book Archive