Antitumor screening procedures of the National Cancer Institute

Area of Science:

• Oncology
• Pharmacology
• Drug Discovery

Background:

• The National Cancer Institute's Drug Development Program has historically utilized in vivo rodent tumor models for evaluating anticancer agents.
• Empirical screening of diverse chemical structures and natural products has been a cornerstone of the program's strategy.
• The evolution of screening models reflects advancements in cancer research and drug development.

Purpose of the Study:

• To review the historical development and evolution of the National Cancer Institute's drug screening protocols.
• To discuss the rationale behind changes in the in vivo tumor models used for evaluating potential antitumor agents.
• To present the results obtained from different screening approaches throughout the program's history.

Main Methods:

• Retrospective analysis of screening data based on the GELLHORN-HIRSCHBERG Report.
• Successive modifications of transplanted rodent tumor systems, including mouse, rat, and hamster models.
• Inclusion of specific tumor models such as Leukemia 1210, Sarcoma 180, Carcinoma 755, WALKER 256, P388, B16 melanoma, and LEWIS lung carcinoma.
• Utilization of xenografts representing major tumor sites in later stages of the program.

Main Results:

• The initial screening spectrum comprised Sarcoma 180, Carcinoma 755, and Leukemia 1210.
• Subsequent modifications involved expanding the panel to include various rodent tumors and specialized models.
• The program transitioned to using P388 as a pre-screen, followed by a panel of transplanted tumors and xenografts.

Conclusions:

• The evolution of screening models demonstrates a strategic adaptation to improve the identification of effective antitumor agents.
• The historical reliance on empirical screening, complemented by rationally designed drugs, has shaped the program's success.
• The discussion will cover the rationale and outcomes of each screening approach implemented since 1955.