System models, assays and endpoint parameters to evaluate anticancer compounds during preclinical screening.

Area of Science:

• Oncology
• Cancer Biology
• Drug Discovery

Background:

• Anticancer therapies aim for selective cancer cell elimination with minimal normal cell toxicity.
• The cancer stem cell (CSC) theory, based on chemo-resistant CSCs, suggested targeting this subpopulation could cure cancer.
• However, experimental data is controversial, leading to new models emphasizing the need to eliminate all cancer cells.

Purpose of the Study:

• To review current systems, assays, and endpoints for anticancer drug screening.
• To propose a more rational drug screening program based on current cancer biology knowledge.
• To address the limitations of current assays that only assess short-term drug activity.

Main Methods:

• Review of existing in vitro and in vivo systems for drug screening.
• Analysis of endpoint parameters used in current anticancer drug testing.
• Discussion of novel cancer biology models and their implications for drug development.

Main Results:

• Current drug screening assays often provide only short-term activity data.
• This limitation contributes to the low approval rate of drugs entering clinical trials.
• A shift towards evaluating drugs that eliminate all cancer cell types is indicated.

Conclusions:

• The classical cancer stem cell theory is being superseded by models requiring "pankiller drugs" that target all cancer cells.
• Developing effective anticancer therapies necessitates a revised screening approach.
• A rational drug screening program should incorporate assessments for complete cancer cell eradication and relapse prevention.