Skip to main content
SpringerLink
Log in

Chemotherapy of ovarian cancer directed by the human tumor stem cell assay

  • Articles
  • Clinical Applicability
  • Published:
Cancer Chemotherapy and Pharmacology Aims and scope Submit manuscript

Summary

The human tumor stem cell assay (HTSCA) has been used to study the in vitro sensitivity rates of anticancer drugs used in the treatment of 115 patients with previously untreated and relapsing ovarian cancer. The data from these studies have identified patterns of cross resistance and residual sensitivity between these agents, and have allowed the prospective selection of single agents possessing in vitro activity for the treatment of 32 patients with relapsing disease. cis-Platinum and vinblastine were the most active agents in vitro against ovarian TCFUs from both previously untreated and relapsing patients. Prior therapy with even one drug was associated with the acquisition of resistance to several classes of compounds (e.g., melphalan resistance was almost always associated with in vitro adriamycin resistance, P>0.001). A clinical trial yielding similar data would have required nearly 450 evaluable ovarian cancer patients. In 11 of 32 patients in vitro testing predicted sensitivity to single agents: eight of these had partial remissions for a predictive accuracy of 73%. In 33 instances the HTSCA had 100% accuracy in predicting the lack of clinical response. Thus, the HTSCA for advanced ovarian cancer appears to have a similar predictive accuracy rate to the estrogen receptor assay for predicting the response to hormonal therapy for disseminated breast cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Alberts DS, Salmon SE, Chen HSG et al. (1980a) In vitro detection of cross-resistance (XR) and sensitivity (S) in relapsing ovarian cancer (OV) with the human tumor stem cell assay (HTSCA). Proc Am Assoc Cancer 21: 725

    Google Scholar 

  2. Alberts DS, Salmon SE, Chen HSG et al. (1980b) Correlative and predictive accuracy of the human tumor stem cell assay (HTSCA) for anticancer drug activity in ovarian (OV) cancer patients (PTS). Proc Am Soc Clin Oncol 21: C-445

    Google Scholar 

  3. Alberts DS, Salmon SE, Chen HSG et al. (1980c) In vitro clonogenic assay for predicting response of ovarian cancer to chemotherapy. Lancet 2: 340–342

    Google Scholar 

  4. Alberts DS, Chen HSG, Salmon SE (1980d) In vitro drug assay: Pharmacologic considerations. In: Salmon SE (ed) Cloning of human tumor stem cells, chap 16. Liss, New York, pp 197–207

    Google Scholar 

  5. Armitage P (1971) Statistical methods in medical research. Halsted Press/Wiley, New York, pp 207–213

    Google Scholar 

  6. Bagley CM, Young RC, Canellow GP, et al (1972) Treatment of ovarian carcinoma: Possibilities for progress. N Engl J Med 287: 856–862

    Google Scholar 

  7. Bolis G, D'Incalci M, Gramellini F, Mangioni C (1978) Adriamycin in ovarian cancer patients resistant to cyclophosphamide. Eur J Cancer 14: 1401–1402

    Google Scholar 

  8. DiMarco A, Aacamone F, Zunio F (1975) Daunomycin (daunorubicin) and adriamycin and structural analogues: Biological activity and mechanism of action. In: Corcoran JW, Hahn FE (eds) Antibiotics, mechanism of action of antimicrobial and antitumor agents, vol III. Springer, Berlin Heidelberg New York, pp 101–128

    Google Scholar 

  9. Ehrlich CE, Einhorn L, Williams SD, Morgan J (1979) Chemotherapy for stage II–IV epithelial ovarian with cis-dichlorodiammineplatinum (II), adriamycin, and cyclophosphamide: A preliminary report. Cancer Treat Rep 63: 281–288

    Google Scholar 

  10. Hamburger AW, Salmon SE (1977) Primary bioassay of human tumor stem cells. Science 197: 461–463

    Google Scholar 

  11. Hamburger AW, Salmon SE, Kim MB et al. (1978) Direct cloning of human ovarian carcinoma cells in agar. Cancer Res 38: 3438–3444

    Google Scholar 

  12. Hubbard SM, Barkes P, Young RC (1978) Adriamycin therapy for advanced ovarian carcinoma recurrent after chemotherapy. Cancer Treat Rep 62: 1375–1377

    Google Scholar 

  13. Kohn KW, Ewing RAG (1976) Effect of pH on the bleomycin-induced DNA single-strand scission in L1210 cells and the relation to cell survival. Cancer Res 36: 3839–3844

    Google Scholar 

  14. McGuire WL (1978) Hormone receptors: Their role in predicting prognosis and response to endocrine therapy. Semin Oncol 5: 428–433

    Google Scholar 

  15. Miller TP, Jones SE, Chester A (1980) Phase II trial of vindesine in the treatment of lymphomas, breast cancer, and other solid tumors. Cancer Treat Rep 64: 1001–1003

    Google Scholar 

  16. Moon TE, Salmon SE, Chen HSG, Alberts DS (1980) Quantitative association between in vitro and in vivo studies. In: Salmon SE (ed) Cloning of human tumor stem cell, chap 17. Liss, New York, pp 209–221

    Google Scholar 

  17. Moon TE, Salmon SE, Alberts DS et al. (1981) Quantitative association between the in vitro human tumor stem cell assay and clinical response to cancer chemotherapy. Cancer Chemother Pharmacol 6: 211–218

    Google Scholar 

  18. Salmon SE (1980) Clinical correlation of drug sensitivity (1980) In: Salmon SE (ed) Cloning of human tumor stem cells. Liss, New York, pp 265–285

    Google Scholar 

  19. Salmon SE, Buick RN (1979) Preparation of permanent slides of intact soft-agar colony cultures of hematopoietic and tumor stem cells. Cancer Res 39: 1133–1136

    Google Scholar 

  20. Salmon SE, Hamburger AW, Soehnlen BJ et al. (1978) Quantitation of differential sensitivity of human tumor stem cells to anticancer drugs. N Engl J Med 298: 1321–1327

    Google Scholar 

  21. Stanhope CR, Smith JP, Rutledge F (1977) Second trial drugs in ovarian cancer. Gynecol Oncol 5: 52–58

    Google Scholar 

  22. Tobias J, Griffiths T (1975) Management of ovarian carcinoma: Current concepts and future prospects. N Engl J Med 294: 818–823

    Google Scholar 

  23. Vistica DT, Toal JN, Rabinovitz M (1978) Amino acid conferred protection against melphalan: Characterization of melphalan transport and correlation of uptake with cytotoxicity in cultural L 1210 murine leukemia cells. Biochem Pharmacol 27: 2865–2870

    Google Scholar 

  24. Vistica DT, Von Hoff DD, Torain B (to be published) Uptake of melphalan by human ovarian carcinoma cells and its relationship to the amino-acid content of ascitic fluid. Cancer Treat Rep

  25. Vogl SE, Berenzweig M, Kaplan BH, Moukhtar M, Bulkin W (1979) The CHAD and HAD regimens in advanced ovarian cancer: Combination chemotherapy including cyclophosphamide, hexamethylmelamine, adriamycin, and cis-dichlorodiammineplatinum(II). Cancer Treat Rep 63: 311–317

    Google Scholar 

  26. Young RC (1975) Chemotherapy of ovarian cancer: Past and present. Semin Oncol 2: 267–276

    Google Scholar 

  27. Young RC, Chabner BA, Hubbard SP et al. (1978) Advanced ovarian adenocarcinoma: A prospective clinical trial of melphalan (l-PAM) versus combination chemotherapy. N Engl J Med 299: 1261–1266

    Google Scholar 

  28. Young RC, von Hoff DD, Gormley P et al. (1979) cis-Dichlorodiammineplatinum (II) for the treatment of advanced ovarian cancer. Cancer Treat Rep 63: 1539–1543

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. The Cancer Center, College of Medicine, University of Arizona, 85724, Tucson, AZ, USA

    David S. Alberts, H. S. George Chen, Sydney E. Salmon, Earl A. Surwit, Laurie Young, Thomas E. Moon & Frank L. Meyskens Jr

  2. Department of Chemical Engineering, College of Mines, University of Arizona, 85724, Tucson, AZ, USA

    H. S. George Chen

  3. Department of Obstetrics and Gynecology, College of Medicine, University of Arizona, 85724, Tucson, AZ, USA

    Earl A. Surwit

Authors
  1. David S. Alberts
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. H. S. George Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sydney E. Salmon
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Earl A. Surwit
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Laurie Young
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Thomas E. Moon
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Frank L. Meyskens Jr
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

Co-investigators from the Arizona-New Mexico Tumor Cloning Group

Additional information

Gerald Altschuler, James R. Bair, James J. Berens, John A. Bruner, Paul H. Duffy, Morris H. Fine, David H. Franks, Gerald F. Giordano, Robert D. Hilgers, Ralph A. Jackson, Stephen J. Ketchel, David K. King, Nicholas J. Mansour, Jr., Louis M. Newton, Herman S. Rhu, Jon P. Rubach, Thomas N. Suciu, Roy S. Weinrach, and Albert G. Wendt

Rights and permissions

Reprints and permissions

About this article

Cite this article

Alberts, D.S., George Chen, H.S., Salmon, S.E. et al. Chemotherapy of ovarian cancer directed by the human tumor stem cell assay. Cancer Chemother. Pharmacol. 6, 279–285 (1981). https://doi.org/10.1007/BF00256981

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00256981

Keywords

Search

Navigation