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In vitro testing of chemotherapeutic combinations in a rapid thymidine incorporation assay
V K Sondak1, E L Korn, D H Kern
1Division of Surgical Oncology, University of Michigan Medical School, Ann Arbor.
Abstract:
A total of 199 solid human tumors were tested with a rapid thymidine incorporation assay for sensitivity to one of several clinically used multi-drug combinations and to each agent in the combination separately. Melanomas, lung and breast cancers accounted for the majority of specimens. In 120 specimens, at least one single agent exhibited in vitro activity (80% or greater inhibition of thymidine incorporation), and in 116 of these (96.7%) the drug combination was active in vitro. In the 79 specimens where no single agent was active in vitro, the combination was also inactive in 62 (78.5%). Overall, there was concordance of in vitro activity of the most active single agent and the combination of agents in 89.5% of specimens tested. A lack of significant in vitro synergy was noted in all of the drug combinations and tumor types tested. Of note is the fact that in 141 of the 199 tests (70.9%) either no drug (n = 79) or only 1 drug (n = 62) demonstrated in vitro activity. We conclude that the rapid thymidine incorporation assay can be used to test for in vitro sensitivity to drug combinations, and that sensitivity to a drug combination can be inferred if a tumor is sensitive to any component drug of the combination.
Insights
This study shows that a rapid thymidine incorporation assay can predict patient response to multi-drug cancer treatments. If a tumor is sensitive to any single drug in a combination, the combination is likely effective.
Area of Science:
- Oncology
- Pharmacology
- Biochemistry
Background:
- Predicting patient response to chemotherapy is crucial for effective cancer treatment.
- In vitro assays offer a method to assess drug sensitivity before clinical application.
Purpose of the Study:
- To evaluate the utility of a rapid thymidine incorporation assay for predicting in vitro sensitivity to multi-drug chemotherapy combinations.
- To determine the concordance between single-agent activity and combination therapy response in solid human tumors.
Main Methods:
- A rapid thymidine incorporation assay was used to test 199 solid human tumors against single agents and multi-drug combinations.
- Tumor specimens included melanomas, lung, and breast cancers.
- In vitro activity was defined as 80% or greater inhibition of thymidine incorporation.
Main Results:
- In 120 specimens, at least one single agent showed in vitro activity, and the drug combination was active in 96.7% of these.
- In 79 specimens with no single-agent activity, the combination was inactive in 78.5%.
- Overall concordance between single-agent and combination activity was 89.5%, with no significant in vitro synergy observed.
Conclusions:
- The rapid thymidine incorporation assay is a viable method for assessing in vitro sensitivity to drug combinations.
- Sensitivity to a drug combination can be inferred from sensitivity to any of its component drugs.
- A significant portion of tested tumors showed limited in vitro activity to single agents or combinations.