Related Experiment Video
Updated: Jul 29, 2026
Depletion of Mouse Cells from Human Tumor Xenografts Significantly Improves Downstream Analysis of Target Cells
Published on: July 29, 2016
Phase II preclinical drug screening in human tumor xenografts: a first European multicenter collaborative study
E Boven1, B Winograd, D P Berger
1Department of Medical Oncology, Free University Hospital, Amsterdam, The Netherlands.
Abstract:
In a European joint project carried out in 6 laboratories a disease-oriented program was set up consisting of a panel of 7 tumor types, each represented by 4 to 8 different human tumor lines, for secondary screening of promising anticancer drugs. Human tumor lines were selected on the basis of differences in histology, growth rate, and sensitivity to conventional cytostatic agents. Xenografts were grown s.c. in nude mice, and treatment was started when tumors reached a mean diameter of 6 mm in groups of mice where at least 6 tumors were evaluable. Drugs were given at the maximum tolerated dose. For evaluation of drug efficacy, median tumor growth curves were drawn, and specific growth delay and treated/control x 100% were calculated. Doxorubicin (8 mg/kg i.v. days 1 and 8) was effective (treated/control < 50%, and specific growth delay > 1.0) in 0 of 2 breast cancers, 1 of 3 colorectal cancers, 2 of 5 head and neck cancers, 3 of 6 non-small cell lung cancers, 4 of 6 small cell lung cancers, 0 of 3 melanomas, and 3 of 6 ovarian cancer lines. Amsacrine (8 mg/kg i.v. days 1 and 8) was not effective, while datelliptium (35 mg/kg i.p. days 1 and 8) was active against 2 of 6 small cell lung cancer lines. Brequinar sodium (50 mg/kg i.p. days 1-5) showed efficacy in 4 of 5 head and neck cancers, 5 of 8 non-small cell lung cancers, and 4 of 5 small cell lung cancer lines. The project has been shown to be a feasible approach. Clinical activity for doxorubicin and inactivity for amsacrine against solid tumor types was confirmed in the human tumor xenograft panel. Additional anticancer drugs will be studied in the European joint project to further define the reliability of this novel, promising screening approach.
Insights
This study established a human tumor xenograft panel for evaluating anticancer drugs. Doxorubicin showed varied efficacy, while brequinar sodium demonstrated promise in head and neck, lung, and small cell lung cancers.
Area of Science:
- Oncology
- Pharmacology
- Cancer Research
Background:
- A European joint project established a disease-oriented program for secondary screening of anticancer drugs.
- The program utilized a panel of 7 human tumor types with 4-8 lines each, selected for diverse histology, growth rates, and chemosensitivity.
Purpose of the Study:
- To evaluate the efficacy of novel anticancer drugs using a standardized human tumor xenograft model.
- To confirm the clinical activity of doxorubicin and amsacrine in solid tumor types.
Main Methods:
- Human tumor xenografts were grown subcutaneously in nude mice.
- Treatment commenced when tumors reached 6 mm diameter, with drugs administered at maximum tolerated doses.
- Drug efficacy was assessed by median tumor growth curves, specific growth delay, and treated/control ratios.
Main Results:
- Doxorubicin showed efficacy in colorectal, head and neck, non-small cell lung, small cell lung, and ovarian cancers, but not breast or melanoma.
- Amsacrine was ineffective across all tested tumor types.
- Datelliptium showed limited activity in small cell lung cancer.
- Brequinar sodium demonstrated significant efficacy in head and neck, non-small cell lung, and small cell lung cancers.
Conclusions:
- The human tumor xenograft panel is a feasible and reliable approach for anticancer drug screening.
- The results confirmed doxorubicin's clinical activity and amsacrine's inactivity against solid tumors.
- Further studies with additional anticancer drugs will refine the reliability of this screening method.
