Skip to main content
SpringerLink
Log in
Book cover

Chemosensitivity pp 3–18Cite as

An Overview of Chemosensitivity Testing

  • Protocol

Part of the book series: Methods in Molecular Medicine™ ((MIMM,volume 110))

Abstract

This overview chapter presents the importance of chemosensitivity testing for screening new therapeutic agents, identifying patterns of chemosensitivity for different types of tumors, establishing patterns of cross-resistance and sensitivity in treatment naive and relapsing tumors; identifying genomic and proteomic profiles associated with sensitivity; correlating in vitro response, preclinical in vivo effect, and clinical outcome associated with a particular therapeutic agent, and tailoring chemotherapy regimens to individual patients. Various assays are available to achieve these end points, including several in vitro clonogenic and proliferation assays, cell metabolic activity assays, molecular assays to monitor expression of markers for responsiveness, development of drug resistance and induction of apoptosis, in vivo tumor growth and survival assays in metastatic and orthotopic models, and in vivo imaging assays. The advantages and disadvantages of the specific assays are discussed. A summary of research areas related to chemosensitivity testing is also included.

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

Protocol
USD   49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Springer Nature is developing a new tool to find and evaluate Protocols. Learn more

References

  1. Kaspers, G., Zwaan, C., Pieters, R., and Veerman, A. (1999) Cellular drug resistance in childhood acute myeloid leukemia: a mini-review with emphasis on cell culture assays. Adv. Exp. Med. Biol. 457, 415–421.

    PubMed  CAS  Google Scholar 

  2. Robert, J. (1999) Chemosensitivity testing: prediction of response to anticancer drugs using in vitro assays. Electronic J. Oncol. 2, 198–210.

    Google Scholar 

  3. Bellamy, W. (1992) Prediction of response to drug therapy of cancer: a review of in vitro assays. Drugs 44, 690–708.

    Article  PubMed  CAS  Google Scholar 

  4. Gercel-Taylor, C., Ackermann, M., and Taylor, D. (2001) Evaluation of cell proliferation and cell death based assays in chemosensitivity testing. Anticancer Res. 21, 2761–2768.

    PubMed  CAS  Google Scholar 

  5. Von Hoff, D., Clark, G., Stogdill, B., et al. (1983) Prospective clinical trial of a human tumor cloning system. Cancer Res. 43, 1926–1936.

    Google Scholar 

  6. Engblom, P., Rantanen, V., Kulmala, J., and Grenman, S. (1996) Paclitaxel and cisplatin sensitivity of ovarian carcinoma cell lines tested with a 96-well plate clonogenic assay. Anticancer Res. 16, 1743–1747.

    PubMed  CAS  Google Scholar 

  7. Weisenthal, L., Marsden, J., Dill, P., and Macaluso, C. (1983) A novel dye exclusion method for testing in vitro chemosensitivity of human tumors. Cancer Res. 43, 749–757.

    PubMed  CAS  Google Scholar 

  8. Kern, D., Drozemuller, C., Kennedy, M., et al. (1985) Development of a miniaturized improved nucleic acid precursor incorporation assay for chemosensitivity testing of human solid tumors. Cancer Res. 45, 5436–5441.

    PubMed  CAS  Google Scholar 

  9. Sondak, V., Bertelson, C., Tanigawa, N., et al. (1984) Clinical correlations with chemosensitivities measured in a rapid thymidine incorporation assay. Cancer Res. 46, 1725–1728.

    Google Scholar 

  10. Kobayashi, H., Higashiyami, M., Minamigawa, K., et al. (2001) Examination of in vitro chemosensitivity test using collagen gel droplet culture method with colorimetric endpoint quantitation. Jpn. J. Cancer Res. 92, 203–210.

    PubMed  CAS  Google Scholar 

  11. Kangas, L., Gronroos, M., and Nieminen, A. (1984) Bioluminesence of cellular ATP: a new method for evaluating cytotoxic agents in vitro. Med. Biol. 62, 338–343.

    PubMed  CAS  Google Scholar 

  12. Csoka, K., Larsson, R., Tholander, B., Gerdin, E., de la Torre, M., and Nygren, P. (1994) Cytotoxic drug sensitivity testing of tumor cells from patients with ovarian carcinoma using the fluorometric microculture cytotoxicity assay (FMCA). Gynecol. Oncol. 54, 163–170.

    Article  PubMed  CAS  Google Scholar 

  13. Rubinstein, L., Shoemaker, R., Pacell, K., Simon, R., and Tosini, S. (1990) Comparison of in vitro anticancer-drug-screening data generated with a tetrazolium assay versus a protein assay against a diverse panel of human tumor cells lines. J. Natl. Cancer Inst. 82, 1113–1118.

    Article  PubMed  CAS  Google Scholar 

  14. Sevin, B., Peng, Z., Perras, J., Panalver, G., and Averette, H. Application of an ATP bioluminescence assay in human tumor chemosensitivity testing. Gynecol. Oncol. 31, 191–204.

    Google Scholar 

  15. Andreotti, P., Cree, I., Kurbacher, C., et al. (1995) Chemosensitivity testing of human tumors using a microplate adenosine triphosphate luminescence assay: clinical correlation for cisplatin resistance of ovarian carcinoma. Cancer Res., 55, 5276–5282.

    PubMed  CAS  Google Scholar 

  16. Steff, A., Fortin, M., Arguin, C., and Hugo, P. (2001) Detection of a decrease in green fluorescent protein fluorescence for the monitoring of cell death: an assay amenable to high-throughput screening technologies. Cytometry 45, 237–243.

    Article  PubMed  CAS  Google Scholar 

  17. Vistica, D., Skehan, P., Scudiero, D., et al. (1991) Tetrazolium-based assays for cellular viability: a critical examination of selected parameters affecting formazan production. Cancer Res. 51, 2515–2520.

    PubMed  CAS  Google Scholar 

  18. Sargent, J. and Taylor, C. Appraisal of the MTT assay as a rapid test of chemosensitivity in acute myeloid leukemia. Br. J. Cancer 60, 206–210.

    Google Scholar 

  19. Hoffman, R. (1991) Three-dimensional histoculture: origins and applications in cancer research. Cancer Cells 3, 86–92.

    PubMed  CAS  Google Scholar 

  20. Singh, B., Li, R., Xyu, L., et al. (2002) Prediction of survival in patients with head and neck cancer using the histoculture drug response assay. Head Neck 24, 437–442.

    Article  PubMed  Google Scholar 

  21. Meitner, P. (1991) The fluorescence cytoprint assay: a new approach to in vitro chemosensitivity testing. Oncology 5, 75–81.

    PubMed  CAS  Google Scholar 

  22. Kern, D. and Weisenthal, L. (1990) Highly specific prediction of antineoplastic drug resistance with an in vitro assay using supra-pharmacologic drug exposures. J. Natl. Cancer Inst. 82, 582–588.

    Article  PubMed  CAS  Google Scholar 

  23. Haroun, R., Clatterbuck, R., Gibbons, M., et al. (2002) Extreme drug resistance in primary brain tumors: in vitro analysis of 64 resection specimens. J. Neurooncol. 58, 115–123.

    Article  PubMed  Google Scholar 

  24. Fenech, M. (2000) The in vitro micronucleus technique. Mutation Res. 455, 81–95.

    PubMed  CAS  Google Scholar 

  25. Fruhauf, J. and Bosanquet, A. (1993) In vitro determination of drug response: a discussion of clinical applications. PPO Updates 7, 1–21.

    Google Scholar 

  26. Clarke, R. (1996) Human breast cancer cell line xenografts as models of breast cancer: the immunobiologies of recipient mice and the characteristics of several tumorigenic lines. Breast Cancer Res. Treat. 39, 69–86.

    Article  PubMed  CAS  Google Scholar 

  27. Hoffman, R. (1999) Orthotopic metastatic mouse models for anticancer drug discovery and evaluation: a bridge to the clinic. Invest. New Drugs 17, 343–359.

    Article  PubMed  CAS  Google Scholar 

  28. Price, J. (1996) Metastasis from human breast cancer cell lines. Breast Cancer Res. Treat. 39, 93–102.

    Article  PubMed  CAS  Google Scholar 

  29. Konovalova, N., Diatchkovskaya, R., Ganieva, L., Volkova, L., Lapshin, I., Rudakov, B., Shaposhnikov, Y., and Shapiro, A. (1991) Subrenal capsule assay of human tumor chemosensitivity. Neoplasma 38, 275–284.

    PubMed  CAS  Google Scholar 

  30. Tomayko, M. and Reynolds, C. (1989) Determination of subcutaneous tumor size in athymic (nude) mice. Cancer Chemother. Pharmacol. 24, 148–154.

    Article  PubMed  CAS  Google Scholar 

  31. Heitjan, D., Manni, A., and Santen, R. (1993) Statistical analysis of in vivo tumor growth experiments. Cancer Res. 53, 6042–6050.

    PubMed  CAS  Google Scholar 

  32. Gibbs, J., Slocum, H., Cao, S., and Rustum, Y. (1999) Image analysis for quantitation of solid tumor drug sensitivity. Int. J. Surg. Invest. 1, 133–138.

    CAS  Google Scholar 

  33. Kubota, K. (2001) From tumor biology to clinical PET: a review of positron emission tomography (PET) in oncology. Ann. Nucl. Med. 15, 471–486.

    Article  PubMed  CAS  Google Scholar 

  34. Belhocine, T., Steinmetz, N., Hustinx, R., et al. (2002) Increased uptake of the apoptosis imaging agent (99m)Tc recombinant human Annexin V in human tumors after one course of chemotherapy as a predictor of tumor response and patient prognosis. Clin. Cancer Res. 8, 2766–2774.

    PubMed  CAS  Google Scholar 

  35. Mazurchuk, R., Glaves, D., and Raghavan, D. (1997) Magnetic resonance imaging of response to chemotherapy in orthotopic xenografts of human bladder cancer. Clin. Cancer Res. 3, 1635–1641.

    PubMed  CAS  Google Scholar 

  36. Nakanishi, H., Mochizuki, Y., Kodera, Y., et al. (2003) Chemosensitivity of peritoneal micrometastases as evaluated using green fluorescence protein (GFP)-tagged human gastric cancer cell line. Cancer Sci. 94, 112–118.

    Article  PubMed  CAS  Google Scholar 

  37. Tewari, K. and Manetta, A. (1999) In vitro chemosensitivity testing and mechanisms of drug resistance. Curr. Oncol. Rep. 1, 77–84.

    Article  PubMed  CAS  Google Scholar 

  38. el-Deiry, W. S. (1997) Role of oncogenes in resistance and killing by cancer therapeutic agents. Curr. Opin. Oncol. 9, 79–87.

    Article  PubMed  CAS  Google Scholar 

  39. Fan, S., el-Deiry, W., Bae, I., et al. (1994) p53 gene mutations are associated with decreased sensitivity of human lymphoma cells to DNA damaging agents. Cancer Res. 54, 5824–5830.

    PubMed  CAS  Google Scholar 

  40. Bosken, C., Wei, Q., Amos, C., and Spitz, M. (2002) An analysis of DNA repair as a determinant of survival in patients with non-small-cell lung cancer. J. Natl. Cancer Inst. 94, 1091–1099.

    PubMed  Google Scholar 

  41. Zunino, F., Perego, P., Pilotti, S., and Pratesi, G. (1997) Role of apoptotic response in cellular resistance to cytotoxic agents. Pharmacol. Ther. 76, 177–185.

    Article  PubMed  CAS  Google Scholar 

  42. Wang, Y., Ashkenazi, Y., and Bachrach, U. In vitro chemosensitivity of hematological cancers: immunohistochemical detection of ornithine decarboxylase. Anticancer Drugs 10, 797–805.

    Google Scholar 

  43. Park, K., Rha, S., Kim, C., et al. (1998) Telomerase activity and telomere lengths in various cell lines: changes of telomerase activity can be another method for chemosensitivity evaluation. Int. J. Oncol. 13, 489–495.

    PubMed  CAS  Google Scholar 

  44. Modrak, D., Rodriguez, M., Goldenberg, D., Lew, W., and Blumenthal, R. (2002) Sphingomyelin enhances chemotherapy efficacy and increases apoptosis in human colonic tumor xenografts. Int. J. Oncol. 20, 379–384.

    PubMed  CAS  Google Scholar 

  45. Epstein, R. (1990) Drug-induced DNA damage and tumor chemosensitivity. J. Clin. Oncol. 8, 2062–2084.

    PubMed  CAS  Google Scholar 

  46. Xia, F. and Powell, S. (2002) The molecular basis of radiosensitivity and chemosensitivity in the treatment of breast cancer. Semin. Radiat. Oncol. 12, 296–304.

    Article  PubMed  Google Scholar 

  47. Manahan, K., Taylor, D., and Gercel-Taylor, C. (2001) Clonal heterogeneity of p53 mutations in ovarian cancer. Int. J. Oncol. 19, 387–394.

    PubMed  CAS  Google Scholar 

  48. Granjean, F., Bremaud, L., Verdier, M., Robert, J., and Ratinaud, M. (2001) Sequential gene expression of P-glycoprotein (P-gp), multidrug resistance associated protein (MRP) and lung resistance protein: functional activity of P-gp and MRP present in the doxorubicin-resistant human K562 cell lines. Anticancer Drugs 12, 247–258.

    Article  Google Scholar 

  49. Michieli, M., Damiani, D., Ermacora, A., et al. (2000) P-glycoprotein (PGP), lung resistance-related protein (LRP) and multidrug resistance-associated protein (MRP) expression in acute promyelocytic leukemia. Br. J. Haematol. 108, 703–709.

    Article  PubMed  CAS  Google Scholar 

  50. Pallis, M., Turzanski, J., Langabeer, S., and Russell, N. (1999) Reproducible flow cytometric methodology for measuring multidrug resistance in leukaemic blasts. Adv. Exp. Med. Biol. 457, 77–88.

    PubMed  CAS  Google Scholar 

  51. Pall, G., Spitaler, M., Hofmann, J., Thaler, J., and Ludescher, C. (1997) Multidrug resistance in acute leukemia: a comparison of different diagnostic methods. Leukemia 11, 1067–1072.

    Article  PubMed  CAS  Google Scholar 

  52. Singh, N. (2000) A simple method for accurate estimation of apoptotic cells. Exp. Cell. Res. 256, 328–337.

    Article  PubMed  CAS  Google Scholar 

  53. Munshi, A., McDonnell, T., and Meyn, R. (2002) Chemotherapeutic agents enhance TRAIL-induced apoptosis in prostate cancer cells. Cancer Chemother. Pharmacol. 50, 46–52.

    Article  PubMed  CAS  Google Scholar 

  54. Maciorowski, Z., Klijanienko, J., Padoy, E., et al. (2001) Comparative image and flow cytometric TUNEL analysis of fine needle samples of breast carcinoma. Cytometry 46, 150–156.

    Article  PubMed  CAS  Google Scholar 

  55. Ogata, S., Okumura, K., and Taguchi, H. (2000) A simple and rapid method for the detection of poly(ADP-ribose) by flow cytometry. Biosci. Biotechnol. Biochem. 64, 510–515.

    Article  PubMed  CAS  Google Scholar 

  56. Nita, M., Nagawa, H., Tominago, O., et al. (1998) 5-Fluorouracil induces apoptosis in human colon cancer cell lines with modulation of Bcl-2 family proteins. Br. J. Cancer 78, 986–992.

    Article  PubMed  CAS  Google Scholar 

  57. Smith, D., Gao, G., Zhang, X., Wang, G., and Dou, Q. (2000) Regulation of tumor cell apoptotic sensitivity during the cell cycle [review]. Int. J. Mol. Med. 6, 503–507.

    PubMed  CAS  Google Scholar 

  58. Sonneveld, P. (2000) Multidrug resistance in hematological malignancies. J. Intern. Med. 247, 521–534.

    PubMed  CAS  Google Scholar 

  59. Staunton, J., Slonim, D., Coller, H., et al. (2001) Chemosensitivity prediction by transcriptional profiling. Proc. Natl. Acad. Sci. USA 98, 10,787–10,792.

    Article  PubMed  CAS  Google Scholar 

  60. Bao, L. and Sun, Z. (2002) Identifying genes related to drug anticancer mechanisms using support vector machine. FEBS Lett. 521, 109–114.

    Article  PubMed  CAS  Google Scholar 

  61. McLeod, H. Individualized cancer therapy: molecular approaches to the prediction of tumor response. Expert Rev. Anticancer Ther. 2, 113–119.

    Google Scholar 

  62. Amundson, S., Myers, T., Scudiero, D., Kitada, S., Reed, J., and Fornace, A. (2000) An informatics approach identifying markers of chemosensitivity in human cancer cell lines. Cancer Res. 60, 6101–6110.

    PubMed  CAS  Google Scholar 

  63. Alizadeh, A., Eisen, M., and Dasvis, R. (2000) Distinct types of diffuse large B-cell lympoma identified by gene expression profiling. Nature 403, 503–511.

    Article  PubMed  CAS  Google Scholar 

  64. Kihara, C., Tsunoda, T., Tanaka, T., et al. (2001) Prediction of sensitivity of esophageal tumors to adjuvant chemotherapy by cDNA microarray analysis of gene-expression profiles. Cancer Res. 61, 6474–6479.

    PubMed  CAS  Google Scholar 

  65. Sotirious, C., Powles, T., Dowsett, M., et al. (2002) Gene expression profiles derived from fine needle aspiration correlate with response to systemic chemotherapy in breast cancer. Breast Cancer Res. 4, R3.

    Article  Google Scholar 

  66. Poland, J., Schadendorf, D., Lage, H., Schnolzer, M., Celis, J., and Siha, P. (2002) Study of therapy resistance in cancer cells with functional proteome analysis. Clin. Chem. Lab. Med. 40, 221–234.

    Article  PubMed  CAS  Google Scholar 

  67. Aschele, C., Debernardis, D., Casazza, S., et al. (1999) Immunohistochemical quantitation of thymidylate synthase expression in colorectal cancer metastases predicts for clinical outcome to fluorouracil-based chemotherapy. J. Clin. Oncol. 17, 1760–1770.

    PubMed  CAS  Google Scholar 

  68. Bachrach, U. and Wang, Y. (2003) In vitro chemosensitivity testing of hematological cancer patients: detection of ornithine decarboxylase. Rec. Results Cancer Res. 161, 62–70.

    CAS  Google Scholar 

  69. Konecny, G., Fritz, M., Untch, M., et al. (2001) Her-2/neu overexpression and in vitro chemosensitivity to CMF and FEC in primary breast cancer. Breast Cancer Res. Treat. 69, 53–63.

    Article  PubMed  CAS  Google Scholar 

  70. Yang, Q., Sakurai, T., Yoshimura, G., et al. (2000) Overexpression of p27 protein in human breast cancer correlates with in vitro resistance to doxorubicin and mitomycin C. Anticancer Res. 20, 4319–4322.

    PubMed  CAS  Google Scholar 

  71. Yang, Q., Sakurai, T., Yoshimura, G., et al. (2000) Expression of Bcl-2 but not Bax or p53 correlates with in vitro resistance to a series of anticancer drugs in breast carcinoma. Breast Cancer Res. Treat. 61, 211–216.

    Article  PubMed  CAS  Google Scholar 

  72. Rozan, S., Vincent-Salomon, A., Zafrani, B., et al. (1998) No significant predictive value of c-erbB-2 or p53 expression regarding sensitivity to primary chemotherapy or radiotherapy in breast cancer. Int. J. Cancer 79, 27–33.

    Article  PubMed  CAS  Google Scholar 

  73. Ginestier, C., Charafe-Jauffret, E., Bertucci, F., et al. (2002) Distinct and complementary information provided by use of tissue and DNA microarrays in the study of breast tumor markers. Am. J. Pathol. 161, 1223–1233.

    Article  PubMed  CAS  Google Scholar 

  74. Jones, M., Krutzsch, H., Shu, H., et al. (2002) Proteomic analysis and identification of new biomarkers and therapeutic targets for invasive ovarian cancer. Proteomics 2, 76–84.

    Article  PubMed  CAS  Google Scholar 

  75. Konecny, G., Untch, M., Slamon, D., et al. (2001) Drug interactions and cytotoxic effects of paclitaxel in combination with carboplatin, epirubicin, gemcitabine, or vinorelbine in breast cancer cell lines and tumor samples. Breast Cancer Res. Treat. 67, 223–233.

    Article  PubMed  CAS  Google Scholar 

  76. Lopez, A., Pegram, M., Slamon, D., and Landaw, E. (1999) A model-based approach for assessing in vivo combination therapy interactions. Proc. Natl. Acad. Sci. USA 96, 13,023–13,028.

    Article  PubMed  CAS  Google Scholar 

  77. Heim, M., Eberhardt, W., Seeber, S., and Muller, M. (2000) Differential modulation of chemosensitivity to alkylating agents and platinum compounds by DNA repair modulators in human lung cancer cell lines. J. Cancer Res. Clin. Oncol. 126, 198–204.

    Article  PubMed  CAS  Google Scholar 

  78. Kondratov, R., Komarov, P., Becker, Y., Ewenson, A., and Gudkov, A. (2001) Small molecules that dramatically alter multidrug resistance phenotype by modulating the substrate specificity of P-glycoprotein. Proc. Natl. Acad. Sci. USA 98, 14,078–14,083.

    Article  PubMed  CAS  Google Scholar 

  79. Henewisch-Becker, S. (1996) MDR1 reversal: criteria for clinical trials designed to overcome the multidrug resistance phenotype. Leukemia 10, S32–S38.

    Google Scholar 

  80. Levi, F., Giacchetti, S., Zidani, R., et al. (2001) Chronotherapy of colorectal cancer metastases. Hepatogastroenterology 48, 320–322.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Garden State Cancer Center, Belleville, NJ, USA

    Rosalyn D. Blumenthal

Authors
  1. Rosalyn D. Blumenthal
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Garden State Cancer Center, Belleville, NJ

    Rosalyn D. Blumenthal

Rights and permissions

Reprints and permissions

Copyright information

© 2005 Humana Press Inc., Totowa, NJ

About this protocol

Cite this protocol

Blumenthal, R.D. (2005). An Overview of Chemosensitivity Testing. In: Blumenthal, R.D. (eds) Chemosensitivity. Methods in Molecular Medicine™, vol 110. Humana Press. https://doi.org/10.1385/1-59259-869-2:003

Download citation

  • DOI: https://doi.org/10.1385/1-59259-869-2:003

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-345-9

  • Online ISBN: 978-1-59259-869-4

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation