Table 3.

Future challenges and possible solutions for mouse preclinical cancer trials

Issue	Challenges	Possible Solutions
Model improvement	More precise spatial and temporal control of genetic alterations in mouse tissues	Improve technologies for genomic editing (e.g., CRISPR) and regulating gene activity
	Human relevance of stroma, immune system and therapeutic targets in mouse cancer models	“Humanize” genes via genetic engineering and immune system by reconstitution with human hematopoietic stem cells
	Recapitulation of the tumor heterogeneity found in human cancers	Introduce environmental etiological factors (e.g., UV in skin cancer models); allow tumor evolution by avoiding inappropriately dominant oncogenic drivers
Study setting	Difficulties in diagnosis and treatment of large cohorts of mice as individual patients	Synchronize tumorigenesis by adopting inducible GEM or transplantable GDA systems
	Disease progression and clinically relevant endpoints in preclinical study	Improve biomarkers and imaging techniques for tumor tracking; adopt clinically-relevant endpoints (e.g., progression-free survival)
	Integration of pathologic, genomic, bioinformatic, molecular and immunological analyses	Develop/share improved and standardized protocols; organize workflows with core facilities
Extrapolation to human disease	Evaluating effects of life style on therapeutic outcomes	Consider gender, diet, and exposure to environmental factors in protocol development; consider effects of microbiota
	Physiological difference between mouse and human	“Humanize” aspects of mice; consider scaling law in PD/PK, life span, hemodynamics, etc.