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[Preclinical screening of chemotherapeutic and endocrine agents using human tumor xenografts--nude mouse system]
1Dept. of Surgery, School of Medicine, Keio University.
Abstract:
Although newly developed antitumor agents had been screened using cultured human cell lines and rodent tumor systems, it was apparent that the positive antitumor activity of the agents on these experimental tumors is not a sufficient but a necessary condition to elucidate the antitumor activity on clinical human cancers. We have clarified that the chemosensitivity of human gastric, breast colon carcinoma xenografts could reproduce the essentially identical chemosensitivity of clinical carcinomas when the maximum tolerable doses of the conventionally available agents were administered to tumor bearing nude mice, and human breast carcinoma xenografts had a similar estrogen dependency and endocrine sensitivity to clinical human breast cancer. These findings indicated that the human tumor xenografts--nude mouse is an appropriate model to predict the clinical antitumor activity of newly developed antitumor agents.
Insights
Newly developed antitumor drugs require accurate prediction models for clinical efficacy. Human tumor xenografts in nude mice effectively mimic patient tumor responses, validating their use in preclinical drug screening.
Area of Science:
- Oncology
- Pharmacology
- Translational Medicine
Context:
- Preclinical screening of novel antitumor agents relies on cell lines and rodent models.
- Existing models often fail to accurately predict clinical efficacy in human cancers.
- There is a critical need for more predictive preclinical models in cancer drug development.
Purpose:
- To evaluate the predictive value of human tumor xenografts in nude mice for clinical antitumor activity.
- To compare the chemosensitivity and endocrine sensitivity of xenografts with clinical human carcinomas.
- To establish the nude mouse xenograft model as an appropriate platform for predicting anticancer drug efficacy.
Summary:
- Human tumor xenografts (gastric, breast, colon) in nude mice demonstrated chemosensitivity mirroring clinical carcinomas when treated with maximum tolerable doses of conventional agents.
- Human breast carcinoma xenografts exhibited estrogen dependency and endocrine sensitivity comparable to clinical counterparts.
- These findings confirm the utility of human tumor xenografts in nude mice for predicting clinical outcomes of novel antitumor agents.
Impact:
- Validates the human tumor xenograft-nude mouse model for preclinical anticancer drug evaluation.
- Enhances the reliability of early-stage drug screening, potentially accelerating the development of effective cancer therapies.
- Provides a more accurate platform for predicting clinical antitumor activity, reducing attrition in later drug development stages.