8. Summary and Prospect
It is undeniable that animal models have played a huge role in revealing the mechanism of tumorigenesis and evaluating new drugs. It not only avoids the huge risks that may be caused by human trials, but also provides a safe and reliable method for leukemia research. More importantly, animal models provide an experimental platform for testing the efficacy of novel therapeutic compounds on human ALL and for studying drug resistance mechanisms. To sumĀ up, these models provide a basis for drug development, screening and testing. And ultimately, they provide a basis for individualized treatment.
The advantage of the spontaneous model is that the clinical symptoms are more similar to those of human tumors, and the conditions for tumor occurrence are more natural. However, the etiology of the spontaneous model is different from that of humans, and is mainly caused by genetic factors. Moreover, this type of model is easily affected by environmental factors, may cause disease complications, and has poor stability. In the past, chemistry, irradiation and viral models have played a significant role in ALL research and have been used to discover and evaluate ALL drugs. The tumorigenesis mechanisms of the induced animal model are clear, and the tumorigenesis rate is relatively high. However, this type of model is unstable and has a high fatality rate. Due to species differences, the pharmacodynamic results of these animal models are not conducive to derivation of human medications. In order to better simulate human diseases, researchers implanted humanized tumor cells into immunodeficient mice and established xenograft models, which have now become the main tool for studying ALL, providing us with the opportunity to observe the entire process of the development and regression of lymphocytic leukemia and may play a crucial role in clinical. The advantages of xenotransplantation are that the model is easy to establish, the speed of tumor formation is fast, and the clinical manifestations are similar to those of human leukemias, especially in terms of histopathology, immunohistochemical phenotype and karyotype. The transgenic model has obvious practicality in preclinical drug efficacy testing and exploring the interaction of matrix-immune cells. The advantages of transgenic models are that, these models overcome the problem that xenograft models cannot better simulate the microenvironment of tumor cell growth, and can accurately simulate human leukemia. These have made transgenic models have been successfully used to screen for and test novel targets and inhibitors. The major disadvantage is that there is a certain difference in interstitial components between mice and humans. In addition, transgenic animals are expensive, and the tumor formation process is complicated. We list the advantages and limitations of the various animal models in Table 1.
Evaluating therapeutic targets in transgenic and xenograft models is expected to enter clinical trials to improve the lives of leukemia patients. In future, advances in genome editing technology and cooperation in multidisciplinary fields will promote the production of more humanized mouse strains, which will help researchers to simulate the complex biology of ALL in mice more accurately. Ultimately, the use of many bioengineering models and continuous efforts to improve their effectiveness and physiological relevance will push preclinical research into a new era of targeted treatment development.