Animal models play an important role in the preclinical evaluation of anti-tumor drugs. The establishment of tumor animal models provide a powerful tool for studying the mechanism of tumorigenesis and metastasis, even validating the efficacy of anti-tumor drugs. Rodent models have many advantages in tumor research, such as fast breeding, low cost, and versatile genetic modification. These traits make them an indispensable tool for preclinical therapeutics screening.
It is necessary to establish precise animal models to gain an accurate understanding of tumor pathogenesis, the host-tumor relationship, the process of tumor invasion and metastasis, and the effectiveness of therapeutic measures. Mice share many similarities with humans, such as in genetics, pathology, and biology, so they are ideal animal models for tumor research. Mouse model is a powerful tool to integrating basic and clinical tumor research and has been used in various fields of oncology.
1. Keep the biological characteristics of primary tumor;
2. The cellular and molecular phenomena associated with tumor growth and metastasis can be studied;
3. Objective and quantitative indicators;
4. Reliability, repeatability, effectiveness, and practicality.
The use of mouse tumor models makes it possible to achieve the replication of human tumors, which greatly shortens the research timeline, and can help researchers observe the whole process of tumor occurrence and development. It is of great significance for the study of the mechanism of tumor development, prevention, and treatment. With the deepening understanding of tumors and the development of experimental zoology, mouse tumor models have been widely used in various tumor research to achieve significant progress in our understanding of tumor pathologies.
① Spontaneous tumor model
② Induced tumor model
③ Transplantation model
④ Genetic engineering model
Spontaneous tumor model refers to the tumor growth naturally in animal model without any artificial interference. The biggest advantage of the spontaneous tumor models is that the tumor completely occurs under natural conditions, excluding human factors and interventions. The occurrence and development of tumor is like that in humans, reflecting the tumor susceptibility of animals and the accumulation of environmental carcinogens and cancer-promoting substances.
The induced mouse tumor model is a mouse model which uses chemical carcinogens to induce the occurrence of tumors. At present, chemical carcinogens such as polycyclic aromatic meridians, nitrosamines, and azo dyes are widely applied in inducing tumor models. The selection of animals and carcinogens is particularly important during the establishment of induced mouse tumor model, and the time and degree of carcinogen induction can be controlled by the carcinogen measurement. For example, a tumor can only be induced in some animals, which is related to the sensitivity of animal species and organs, so there is a great difference among species. If the skin cancer is induced by aromatic vertical carcinogens, mouse is the best choice, but it is difficult to induce skin cancer in rats. The carcinogens of nitrosamines can induce esophageal cancer in rats, while only pre gastric cancer can be induced in mice.
The transplantation model is formed by transplanting tumor tissue or cells (from animal or human) into the body of the model animal. According to different recipient animals, transplanted tumor models can be divided into normal animal transplanted tumor model and immunodeficient animal transplanted tumor model. Additionally, the source of the tumor tissue determines whether the transplant model is a homograft (same species) or xenograft (different species). Homograft mouse models involves a transplant of tumor tissue into homologous or allogeneic recipient mice, while xenograft mouse model are made by transplanting human tumor tissues into mice to make it grow and develop.
Common xenograft models are outlined below:
Patient derived xenografts (PDX) model is a tumor model established by transplanting fresh tumor tissue from patients into immunodeficient mice.
Cell line-derived xenograft (CDX) model is a tumor model constructed by transplanting human- or mouse-derived tumor cell lines into immunodeficient mice. As a classical in vivo experimental method, cell line-based tumor models have been widely utilized in oncology research and anti-tumor drug development.
The establishment of genetically engineered and transgenic tumor animal models has become much easier with recent advancements in molecular cloning and microinjection technologies. Studies have found that overexpression, deletion, or mutation of a gene can lead to tumor development in mice. Therefore, we can use genetic engineering methods to introduce oncogenes or knock out tumor suppressor genes to establish genetically modified mouse models of spontaneous or induced tumors, and then carry out corresponding experiments with the model.
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