Orthotopic models in cancer research: a literature review. To the 150th anniversary of the first successful serial tumor transplantation in animals

Background. Transplantation models, including allografts and xenografts are crucial in oncology research because they help study the mechanisms of carcinogenesis and assess the activity of promising antitumor agents.

Objectives: 1) to conduct a traditional analysis of scientific literature devoted to orthotopic transplantation in laboratory animals using various sources of tumor material, 2) to describe the main advantages and limitations of orthotopic models, 3) to provide practical recommendations for researchers dealing with orthotopic transplantation models.

Material and Methods. A search was conducted in PubMed and Google Scholar bibliographic databases. The review included relevant publications available for search until April 30, 2025.

Results. Compared to transplantation of tumor cell suspensions cultured in vitro, transplantation of solid tumor fragments ensures preservation of the clonal heterogeneity of the tumor, components of its microenvironment and extracellular matrix, which support engraftment and tumor growth. Compared to subcutaneous transplantation, orthotopic models offer a more realistic depiction of the complex interactions in the tumor-host system and the pathological characteristics of human cancers, particularly those involving metastasis. Because orthotopic tumors exist within their natural environment, the evaluation of their response during preclinical research is more likely to be translatable in the initial phases of clinical trials.

Conclusion. Incorporating orthotopic models into non-clinical in vivo pharmacodynamic research programs improve the predicitve value and dependability of preclinical results and offer a chance to gain a more thorough understanding of the antitumor activity of the experimental treatment.

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