Studying drug resistance using genetically engineered mouse models for breast cancer
Sven Rottenberg1, Marina Pajic, Jos Jonkers
1Division of Molecular Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands. s.rottenberg@nki.nl
Methods in Molecular Biology (Clifton, N.J.)
|December 2, 2009
Summary
Genetically engineered mouse models (GEMMs) offer powerful tools to study breast cancer drug resistance. These models allow researchers to investigate resistance mechanisms in vivo with accessible tumors and modified cells.
Area of Science:
- Oncology
- Genetics
- Pharmacology
Background:
- Genetically engineered mouse models (GEMMs) are crucial for studying human diseases in vivo.
- Breast cancer drug resistance remains a significant clinical challenge.
- Understanding resistance mechanisms is key to developing effective therapies.
Purpose of the Study:
- To provide an overview of experimental approaches using GEMMs to study breast cancer drug resistance.
- To detail methods for investigating drug resistance mechanisms in vivo.
- To highlight the advantages of GEMMs for breast cancer research.
Main Methods:
- Utilizing GEMMs that accurately mimic human breast cancer.
- Employing accessible mammary tumors for pre- and post-treatment sampling.
- Performing orthotopic transplantation of tumors into syngeneic animals.
- Modifying tumor cells in vitro (gene overexpression, shRNA knockdown, insertional mutagenesis) prior to transplantation.
Main Results:
- GEMMs provide a controlled environment to study drug resistance, minimizing genomic heterogeneity.
- Superficial mammary tumors allow for serial measurements and sampling.
- In vitro modifications enable precise investigation of genetic alterations driving resistance.
- Orthotopic transplantation models recapitulate the tumor microenvironment.
Conclusions:
- GEMMs are invaluable tools for dissecting the complex mechanisms of breast cancer drug resistance.
- These models facilitate the development and testing of novel therapeutic strategies.
- GEMMs advance our understanding of in vivo drug resistance, paving the way for improved patient outcomes.
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