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Updated: Jul 16, 2026

Generation of Genetically Modified Mice through the Microinjection of Oocytes
Published on: June 15, 2017
Harnessing genetically engineered mouse models for preclinical testing
Ana I Robles1, Lyuba Varticovski
1Laboratory of Human Carcinogenesis, Center for Cancer Research, NCI, NIH, 37 Convent Drive, Room 3060, Bethesda, MD 20892, United States.
Abstract:
Recent studies cast doubt on the value of traditionally used models as tools for testing therapies for human cancer. Although the standard practice of xenografting tumors into immunocompromised mice generates reproducible tumors, drug testing in these models has low predictive power when compared to the clinical responses in Phase II trials. The use of tumor-bearing genetically engineered mouse models holds promise for improving preclinical testing. These models recapitulate specific molecular pathways in tumor initiation or progression and provide a biological system in which to study the disease process for assessing efficacy of new therapies and proof-of-principle for testing molecularly targeted drugs. In this review, we discuss the advantages and limitations of genetically engineered mice and plausible solutions for adapting these valuable tumors for wider use in preclinical testing by transplantation into naïve recipients. We also provide examples of comparative molecular analysis of mammary tumors from MMTV-Polyoma Middle-T antigen and MMTV-wnt1 models as tools for finding clinical correlates, validating existing models and guiding the development of new genetically engineered mouse models for cancer.
Insights
Genetically engineered mouse models offer better cancer therapy testing than traditional xenografts. Adapting these models through transplantation can improve preclinical drug development and clinical trial success.
Area of Science:
- Oncology
- Preclinical Cancer Research
- Translational Medicine
Background:
- Traditional xenograft models show low predictive power for human cancer drug responses.
- Genetically engineered mouse models (GEMMs) better recapitulate cancer molecular pathways.
Purpose of the Study:
- To review the advantages and limitations of GEMMs for cancer therapy testing.
- To propose solutions for adapting GEMMs for broader preclinical use.
- To guide the development of new GEMMs for cancer research.
Main Methods:
- Discussion of advantages and limitations of GEMMs.
- Exploration of tumor transplantation techniques for GEMMs.
- Comparative molecular analysis of mammary tumors from MMTV-Polyoma Middle-T antigen and MMTV-wnt1 models.
Main Results:
- GEMMs offer improved biological systems for studying cancer progression.
- Transplantation of GEMM tumors into naïve recipients is a plausible adaptation strategy.
- Comparative molecular analysis aids in validating models and identifying clinical correlates.
Conclusions:
- GEMMs hold significant promise for enhancing preclinical cancer therapy testing.
- Adapting GEMMs via transplantation can increase their utility in drug development.
- Further development and validation of GEMMs are crucial for advancing cancer research.
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