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Three tumor sensitivity tests evaluated with mouse tumors
Abstract:
The predictive value of three types of tumor sensitivity tests was evaluated using mouse tumors. Sensitivities of osteosarcoma C22LR, Lewis lung and M2661 carcinoma were determined for the following drugs: DNA interacting or alkylating agent (doxorubicin, cisplatin, 1,3-bis(2-chloroethyl)-1-nitrosourea, melphalan), antimetabolite (5-fluorouracil, methotrexate) and microtubule inhibitor (vinblastine, vincristine). Volume measurements of the subcutaneously growing tumors after treatment with the same drugs were considered to be the traditional reference system with which the results of the in vitro clonogenic assay, the labeled precursor incorporation assay and the subrenal capsule assay were compared. Results obtained with the in vitro clonogenic assay were highly reproducible. With the 1-h drug exposure technique the predictive accuracy was 71%. This result is in the same range as those found by others for human tumors. Predictive accuracy after continuous drug exposure was only 25%. Vinblastine, vincristine and cisplatin caused no inhibition of labeled precursor incorporation. However, the assay is too unreliable to use, due to the extreme variability when used with the other drugs. From 31 consecutively performed duplicate tests in the subrenal capsule assay, nine showed opposite results. This degree of disagreement between duplicate test results was considered too high to make reliable predictions of tumor sensitivity with this assay.
Insights
The in vitro clonogenic assay shows 71% predictive accuracy for mouse tumor sensitivity to chemotherapy after short drug exposure. Other tested assays, like labeled precursor incorporation and subrenal capsule assays, were found unreliable for predicting tumor drug response.
Area of Science:
- Oncology
- Pharmacology
- Experimental Medicine
Background:
- Accurate prediction of tumor sensitivity to chemotherapy is crucial for effective cancer treatment.
- Several in vitro and ex vivo assays are used to predict drug response, but their reliability varies.
Purpose of the Study:
- To evaluate the predictive value of three tumor sensitivity tests: in vitro clonogenic assay, labeled precursor incorporation assay, and subrenal capsule assay.
- To compare the accuracy of these assays against traditional volume measurements in mouse tumor models.
Main Methods:
- Mouse tumor models (osteosarcoma C22LR, Lewis lung, M2661 carcinoma) were treated with various chemotherapy drugs (DNA interacting agents, antimetabolites, microtubule inhibitors).
- Tumor sensitivity was assessed using in vitro clonogenic assay, labeled precursor incorporation assay, and subrenal capsule assay.
- Results were compared to traditional tumor volume measurements post-treatment.
Main Results:
- The in vitro clonogenic assay demonstrated high reproducibility and 71% predictive accuracy with a 1-hour drug exposure, comparable to human tumor studies.
- Predictive accuracy of the in vitro clonogenic assay dropped to 25% with continuous drug exposure.
- The labeled precursor incorporation assay showed unreliable results due to high variability.
- The subrenal capsule assay exhibited significant disagreement between duplicate tests (9 out of 31), rendering it unreliable for prediction.
Conclusions:
- The in vitro clonogenic assay, particularly with short drug exposure, is a reproducible and potentially valuable tool for predicting tumor sensitivity.
- The labeled precursor incorporation and subrenal capsule assays are currently too unreliable for clinical prediction of chemotherapy response.
- Further optimization of predictive assays is needed to improve personalized cancer treatment strategies.