Mouse models in oncogenesis and cancer therapy

Area of Science:

• Oncology
• Translational Research
• Preclinical Cancer Models

Background:

• Animal models are vital for cancer research but require improvement for clinical relevance.
• Metastasis is a key determinant of cancer progression and patient survival, necessitating accurate modeling.
• Genetically modified (GM) mouse models often fail to replicate human cancer's advanced stages and metastatic patterns.

Purpose of the Study:

• To evaluate the relevance of current animal models in cancer research and drug development.
• To compare the utility of genetically modified mice versus orthotopic xenografts for modeling human cancers.
• To assess the potential of orthotopic xenografts in predicting clinical response to antitumor agents.

Main Methods:

• Review of genetically modified (GM) mouse models for cancer research.
• Analysis of orthotopic (ORT) xenografts using human tumor cells in nude mice.
• Evaluation of ex vivo genetic manipulation of human tumor cells for ORT model development.

Main Results:

• GM mice are limited in replicating advanced human cancers and metastatic rates.
• Orthotopic xenografts (ORT) of human tumors in nude mice better reproduce human tumor histology and metastasis.
• ORT models allow for molecular dissection of metastasis and in vivo therapy evaluation, but not early tumorigenesis or immune response.

Conclusions:

• Orthotopic xenografts offer a more promising preclinical model than GM mice for advanced cancer and therapy response.
• Current animal models, including GM mice and ORT xenografts, have limitations in fully predicting clinical outcomes.
• Future advancements in humanizing mouse models may require integrating multiple existing methodologies.