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Updated: Oct 17, 2025
A Protocol for Using Gene Set Enrichment Analysis to Identify the Appropriate Animal Model for Translational Research
Published on: August 16, 2017
Criteria to make animal studies more relevant to treating human cancer
Steven P Wolf1, Frank T Wen2, Hans Schreiber3
1Department of Pathology, The University of Chicago, Chicago, IL, 60637, USA; David and Etta Jonas Center for Cellular Therapy, The University of Chicago, Chicago, IL, 60637, USA.
Abstract:
Certain aspects of experimental tumor models in mice most accurately reflect the biology and immunology of cancer in patients. A survey of experimental cancer immunotherapy papers published in 2020 shows most do not achieve cancer shrinkage although treatment is initiated at an early time point after cancer cell injection, which does not reflect cancer immunotherapy in patients. Even then, few current experimental approaches eradicate the injected malignant cells, most only delay outgrowth. The value of targeting mutation-encoded tumor-specific antigens becomes increasingly evident while problems of finding normal gene-encoded tumor-associated antigens as safe, effective targets persist. It might be time to refocus on realistic experimental settings and truly cancer-specific targets. These antigens are associated with the least risk of side effects.
Insights
Experimental cancer immunotherapy models in mice often fail to reflect patient treatments, with most therapies only delaying tumor growth instead of eradicating it. Focusing on truly cancer-specific targets may improve efficacy and reduce side effects.
Area of Science:
- Oncology
- Immunology
- Translational Research
Background:
- Experimental tumor models in mice are crucial for understanding cancer biology and immunology.
- Current preclinical cancer immunotherapy research often uses models that do not accurately reflect clinical scenarios.
- Many studies initiate treatment at early stages, which differs from patient treatment timelines.
Purpose of the Study:
- To evaluate the alignment of current experimental cancer immunotherapy models with clinical realities.
- To assess the effectiveness of common experimental approaches in achieving tumor regression or eradication.
- To highlight the importance of selecting appropriate targets for effective cancer immunotherapy.
Main Methods:
- Survey of experimental cancer immunotherapy papers published in 2020.
- Analysis of treatment initiation timing in preclinical models versus patient care.
- Evaluation of outcomes such as cancer shrinkage, eradication, and delayed outgrowth.
Main Results:
- Most experimental cancer immunotherapies surveyed did not achieve significant cancer shrinkage, even when treatment started early.
- Few experimental approaches successfully eradicated injected malignant cells, with most merely delaying tumor outgrowth.
- Targeting mutation-encoded tumor-specific antigens shows increasing promise, unlike tumor-associated antigens derived from normal genes.
Conclusions:
- Current experimental cancer models and targets may not adequately predict clinical immunotherapy outcomes.
- There is a need to refine experimental settings to better mirror patient conditions for more relevant research.
- Prioritizing truly cancer-specific targets, such as mutation-encoded antigens, is essential for developing safer and more effective immunotherapies with minimal side effects.
