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.