Methodological aspects of creation of patient-derived tumor xenografts

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Abstract

High rates of cancer incidence and mortality from malignant neoplasms remains an urgent health problem. The development of the most effective therapeutic algorithms is required to improve the survival of cancer patients. An important condition for the discovery of new anticancer drugs and their translation into clinical practice involves the ability to model tumor growth, reproduce the characteristics of human disease, and evaluate measurable effects of pharmacological substances in laboratory facilities. Xenograft models established by direct implantation of fresh tumor tissue samples from individual patients into immunodeficient mice are considered suitable for both preclinical trials and for solving fundamental problems in oncology. The review highlights the significance of patient-­derived xenograft models as a platform with high predictive value and the prerequisites that make them the preferred tool for research in cancer biology. The most important methodological aspects in the creation of these models are considered. Methods for obtaining and preparing biological tumor samples for xenotransplantation are discussed. The significance of the immune status, as well as the phenotypic and genetic characteristics of recipient animals, is described. The article presents the limitations of animal models associated with their immunodeficiency status and ways to overcome them. The principles for choosing xenotransplantation sites (heterotopic and orthotopic) and their advantages and disadvantages are discussed. In conclusion, we emphasize the need to continue the work on optimizing PDX (Patient-Derived Xenograft) models to overcome their limitations and to obtain the most reliable and valuable research results in oncology.

About the authors

A S Goncharova

National Medical Research Centre for Oncology

Author for correspondence.
Email: fateyeva_a_s@list.ru
Russian Federation, Rostov-on-Don, Russia

A N Shevchenko

National Medical Research Centre for Oncology

Email: onko-sekretar@mail.ru
Russian Federation, Rostov-on-Don, Russia

I R Dashkova

National Medical Research Centre for Oncology

Email: onko-sekretar@mail.ru
Russian Federation, Rostov-on-Don, Russia

A E Anisimov

National Medical Research Centre for Oncology

Email: onko-sekretar@mail.ru
Russian Federation, Rostov-on-Don, Russia

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