Developmental therapeutics program at the NCI: molecular target and drug discovery process

Area of Science:

• Oncology
• Pharmacology
• Drug Discovery

Background:

• The National Cancer Institute (NCI) Developmental Therapeutics Program (DTP) supports the development of anticancer and anti-AIDS therapeutic agents.
• DTP aims to translate molecular discoveries into public health medicines.
• DTP manages a repository of natural and synthetic compounds for anticancer evaluation.

Purpose of the Study:

• To describe the DTP's drug discovery and development processes.
• To highlight the unique in vitro and in vivo screening methodologies employed by DTP.
• To showcase the advancement of promising drug candidates for cancer treatment.

Main Methods:

• Utilizing a repository of over 600,000 compounds for evaluation.
• Implementing a unique, high-volume in vitro anticancer drug cell line screen emphasizing human solid tumor cells.
• Employing the hollow fiber assay for initial in vivo efficacy assessment of promising compounds.

Main Results:

• The DTP's screening approach shifted from compound-oriented to disease-panel oriented, using human tumor cells.
• The in vitro screen minimizes animal use and material requirements.
• The hollow fiber assay provides quantitative in vivo efficacy data efficiently.
• Promising agents like flavopiridol, UCN-01, and depsipeptide are being developed for hematopoietic neoplasms.

Conclusions:

• DTP's innovative screening strategies accelerate the discovery and development of novel cancer therapeutics.
• The program effectively identifies and advances potential anticancer drugs with unique mechanisms of action.
• DTP plays a crucial role in translating cancer research into clinical applications.