Models of metastasis in drug discovery

Area of Science:

• Oncology
• Translational Research
• Drug Discovery

Background:

• Metastasis is the primary cause of cancer mortality but is underrepresented in drug discovery.
• Current animal models often fail to accurately approximate clinical metastasis.
• There is a need to integrate metastasis into drug discovery paradigms.

Purpose of the Study:

• To highlight the critical role of metastasis in cancer mortality.
• To advocate for the inclusion of metastasis models in drug discovery and development.
• To provide protocols for utilizing metastasis models in translational studies.

Main Methods:

• Utilizing orthotopic and spontaneous metastasis models (syngeneic and xenogeneic).
• Incorporating host-tumor microenvironmental interactions.
• Employing autochthonous and/or genetically engineered models (GEMs).
• Using resected, orthotopic primary tumors and clinically relevant outcomes.

Main Results:

• The proposed approach integrates metastasis into drug discovery alongside pharmacology and toxicity.
• The chapter provides protocols for metastasis models applicable to translational research.
• This framework enables a rational and hierarchical evaluation of anti-metastatic strategies.

Conclusions:

• Metastasis models are essential for accurate preclinical cancer drug development.
• Integrating metastasis into drug discovery will improve the clinical relevance of new therapies.
• The presented protocols facilitate the use of metastasis models in translational studies.