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Effects of suramin on in vitro growth of fresh human tumors
1Arizona Cancer Center, Tucson 85724.
Background:
Suramin is a polysulfonated urea recently tested in clinical trials as an anticancer agent.
Purpose:
To define tumor types for further clinical testing of suramin, we assessed the in vitro activity of suramin against fresh human tumor specimens.
Methods:
Inhibition of tumor colony formation (human tumor clonogenic assay [HTCA] method) and inhibition of tritiated thymidine incorporation (TTI method) were used as indicators of drug sensitivity.
Results:
With the use of the HTCA method, 80% or more of carcinomas of the colon, endometrium, kidney, lung (non-small-cell), and ovary as well as malignant melanoma and mesothelioma were sensitive to 200 micrograms/mL of suramin by continuous exposure. Suramin's antitumor activity was dose dependent, and it was less effective when tested at concentrations of 50 micrograms/mL or less. With the TTI method, the more slowly growing tumors (breast cancer, colon cancer, multiple myeloma, non-Hodgkin's lymphoma, prostate cancer, and sarcoma) appeared to be less sensitive to suramin. However, when the two assay methods were directly compared in melanoma and ovarian cancer specimens, individual tumors were generally more sensitive to suramin (greater inhibition relative to control) using the HTCA method, whereas the TTI method appeared to underestimate suramin's antitumor activity. There was no significant difference in the activity of suramin when tested in the presence of 10% versus 50% serum.
Conclusion:
These results provide an experimental basis for clinical evaluations of suramin therapy in patients with colon, endometrial, kidney, non-small-cell lung, and ovarian cancers as well as malignant melanoma and mesothelioma.
Insights
Suramin shows significant anticancer activity in vitro against colon, endometrial, kidney, non-small-cell lung, and ovarian cancers, as well as melanoma and mesothelioma. The human tumor clonogenic assay (HTCA) method is more effective in determining suramin sensitivity than the tritiated thymidine incorporation (TTI) method.
Area of Science:
- Oncology
- Pharmacology
- Cancer Research
Background:
- Suramin, a polysulfonated urea, has been investigated as a potential anticancer agent.
- Previous studies have explored suramin's efficacy in clinical trials.
Purpose of the Study:
- To identify specific tumor types responsive to suramin for future clinical trials.
- To assess the in vitro anticancer activity of suramin against diverse human tumor specimens.
Main Methods:
- Utilized the human tumor clonogenic assay (HTCA) to evaluate tumor colony formation inhibition.
- Employed the tritiated thymidine incorporation (TTI) method to measure drug sensitivity.
- Compared the efficacy of HTCA and TTI methods in assessing suramin's activity.
Main Results:
- The HTCA method indicated sensitivity to suramin (200 µg/mL) in 80% of colon, endometrial, kidney, non-small-cell lung, and ovarian carcinomas, as well as malignant melanoma and mesothelioma.
- Suramin's antitumor activity demonstrated a dose-dependent relationship, with reduced efficacy at concentrations ≤50 µg/mL.
- The TTI method appeared to underestimate suramin's activity, particularly in slower-growing tumors, while HTCA provided a more accurate measure of sensitivity.
Conclusions:
- The findings support clinical evaluations of suramin therapy for specific cancers including colon, endometrial, kidney, non-small-cell lung, and ovarian cancers.
- Malignant melanoma and mesothelioma are also identified as potential candidates for suramin treatment based on in vitro sensitivity.
- The HTCA method is recommended for assessing suramin sensitivity in future clinical studies due to its superior accuracy compared to the TTI method.
