Related Experiment Videos
Activity of the multitargeted antifolate LY231514 in the human tumor cloning assay
C D Britten1, E Izbicka, S Hilsenbeck
1University of Texas at San Antonio and Institute for Drug Development, Cancer Therapy and Research Center, 78229, USA.
Purpose:
This study was performed to evaluate the activity of the multitargeted antifolate (MTA or LY231514) against a broad range of human tumors taken directly from patients.
Materials And Methods:
Human tumor colony-forming units were treated with MTA at concentrations of 0.1, 1.0, and 10 microg/ml in 1-h exposure studies. The responses of a limited number of specimens were also evaluated concurrently in 1-h exposures to cisplatin, fluorouracil, irinotecan, and/or paclitaxel.
Results:
Of 358 specimens plated in the 1-h exposure studies, 148 (41%) were evaluable. Overall, responses were observed in 3% of specimens (4/144) at 0.1 microg/ml, 11% (17/148) at 1.0 microg/ml, and 23% (33/141) at 10 microg/ml. In this range of concentrations achievable clinically, there was a significant concentration-response relationship. At 10 microg/ml in the 1-h exposure studies, the response rate in colorectal cancer specimens was 32% (9/28), and the response rate in non-small-cell lung cancer was 25% (6/24). Responses were also observed in several chemoresistant tumors, including renal cell carcinoma, hepatocellular carcinoma, mesothelioma, and pancreatic carcinoma. The activity of MTA was not completely cross-resistant with that of cisplatin, fluorouracil, irinotecan, and paclitaxel.
Conclusions:
MTA demonstrated in vitro activity against a spectrum of tumors, including several tumors generally considered chemoresistant.
Insights
Multitargeted antifolate (MTA) shows promising in vitro activity against various human tumors, including chemoresistant types. This study evaluated MTA
Area of Science:
- Oncology
- Pharmacology
- Cancer Research
Background:
- Multitargeted antifolate (MTA) is a novel antifolate agent.
- Evaluating the in vitro activity of MTA against diverse human tumors is crucial for understanding its therapeutic potential.
Purpose of the Study:
- To assess the efficacy of multitargeted antifolate (MTA) against a wide array of human tumors.
- To determine the dose-response relationship of MTA in vitro.
- To compare MTA's activity with established chemotherapy agents.
Main Methods:
- Human tumor colony-forming units were exposed to MTA at varying concentrations (0.1, 1.0, 10 microg/ml) for 1 hour.
- Concurrent 1-hour exposures to cisplatin, fluorouracil, irinotecan, and/or paclitaxel were performed on a subset of specimens.
- Tumor response rates were evaluated based on colony formation.
Main Results:
- A significant concentration-response relationship was observed for MTA, with response rates of 3%, 11%, and 23% at 0.1, 1.0, and 10 microg/ml, respectively.
- At 10 microg/ml, MTA showed response rates of 32% in colorectal cancer and 25% in non-small-cell lung cancer.
- MTA demonstrated activity against chemoresistant tumors, including renal cell carcinoma, hepatocellular carcinoma, mesothelioma, and pancreatic carcinoma, and was not completely cross-resistant with other agents.
Conclusions:
- MTA exhibits significant in vitro anticancer activity across a broad spectrum of human tumors.
- The drug shows particular promise against chemoresistant malignancies.
- These findings support further investigation of MTA in clinical settings for various cancer types.