Overview of Preclinical Drug-Resistant Tumor Models and Their Application in Drug Discovery

Area of Science:

• Oncology
• Translational Medicine
• Drug Discovery

Background:

• Cancer drug resistance is a major cause of treatment failure and relapse.
• Effective preclinical models are essential for understanding resistance mechanisms and developing new therapeutic strategies.

Purpose of the Study:

• To compare three classes of preclinical cancer models: patient-derived xenografts, induced-resistance models, and engineered isogenic cell lines.
• To summarize resistance mechanisms and therapeutic approaches informed by these models.

Main Methods:

• Comparative analysis of clinical patient-derived xenografts, in vivo/in vitro induced-resistance models, and engineered isogenic cell lines.
• Review of key resistance mechanisms and potential therapeutic strategies.

Main Results:

• Patient-derived xenografts retain tumor heterogeneity and can reflect patient resistance.
• Induced-resistance models recapitulate tumor evolution under therapy.
• Engineered isogenic cell lines isolate specific resistance drivers.

Conclusions:

• Integrating diverse preclinical models accelerates mechanistic insights into cancer drug resistance.
• These models inform the development of combination therapies, targeted inhibitors, and immune-based strategies to overcome resistance.
• This overview aids in selecting appropriate preclinical models and designing strategies to combat cancer drug resistance.