Высокой уровень заболеваемости и смертности от злокачественных новообразований делает разработку новых терапевтических препаратов актуальной задачей современной медицины. Чтобы потенциал научных открытий мог быть реализован в клинической практике, важным условием является доступ к биологическим образцам и их сопроводительным данным для тщательной оценки потенциальной терапевтической мишени, ее связи с конкретным заболеванием и выраженностью противоопухолевого ответа при воздействии изучаемым препаратом. Развитие биомедицинских технологий привело к созданию биобанков, специализирующихся на хранении коллекций препаратов, включающих как образцы тканей пациентов, а именно биопсийные и хирургические фрагменты опухолевых и нормальных тканей, серийные пробы крови, парафиновые блоки, так и производные от них биообразцы, такие как клеточные линии, органоиды, ксенотрансплантаты. В данной статье представлен обзор биобанков, имеющих наиболее обширные аннотированные коллекции опухолевых образцов, в том числе ксенотрансплантатов, полученных от пациентов, описан алгоритм поиска необходимой опухолевой модели при помощи глобального каталога PDX Finder, обсуждается развитие направлений, связанных с созданием и хранением коллекций биопрепаратов для их применения в трансляционных исследованиях в области онкологии. Ключевые слова: онкология, биобанк, репозиторий, PDX-биобанк.

Gastric cancer (GC) is a group of malignant tumors originating from the gastric mucosa cells. The highest incidence of GC is recorded in Japan, China and Russia, and the lowest one in the USA and New Zealand. Extensive molecular genetic research of GC has revealed its heterogeneity associated with the genomic instability of the tumor and the complexity of its phenotype due to simultaneous changes in several oncogenes and suppressors. This was the basis for the creation of the GC classification by molecular subtypes. The creation of a realistic preclinical model is essential for translational GC studies. Cancer cell lines and xenografts derived from them are among the most common preclinical models. They are easy to generate, but they also have limitations, since these models cannot sufficiently reproduce the unique characteristics of each cancer patient. Patient-derived xenografts (PDX) are currently the best model for testing targets and predictors of response to therapy. PDX models are created by transplanting surgically resected human tumors into immunodeficient mice. These models maintain morphological similarity and replicate the molecular characteristics of parental tumors providing an indispensable tool for assessing anticancer drug response. Statistical data from preclinical studies with PDX models can significantly save the time and resources required for clinical trials. Transgenic and knockout mouse models are also widely used in scientific laboratories in order to study specific genetic pathways of oncogenesis and develop experimental therapy for GC. This review discusses the molecular classifications of GC and experimental murine models that reproduce cancer in situ and are a universal platform for preclinical research in experimental oncology.

Purpose of the study. Was to analyze antitumor efficacy of the XAV 939 Wnt signaling pathway inhibitor and its combination with 5 fluorouracil in subcutaneous xenografts derived from patients with colorectal cancer.Materials and methods. Antitumor efficacy of the agents and their combination was studied in xenografts derived from patients with colorectal cancer and subcutaneously implanted in immunodeficient Balb/c Nude mice. All animals with tumors were divided into 4 groups (n = 5): group 1 received 5 fluorouracil 25 mg/kg, group 2 – XAV 939 25 mg/kg, group 3–5 fluorouracil and XAV 939 combination at the same dosages, group 4 was control. Criteria for the efficacy of the tested agents and their combination included tumor growth rate and tumor growth inhibition rate (TGI %).Results. The mean volumes of xenografts and tumor growth rate in the group receiving a combination of 5 fluorouracil and XAV 939 were 335.2 ± 40.7 mm3 , being lower than the averages of xenografts in controls – 609.3 ± 69.5 mm3 (p < 0.05). The mean volumes of xenografts in the group receiving 5 fluorouracil monotherapy were 601.9 ± 45.5 mm3 , in the group with the XAV 939 monotherapy – 527.9 ± 258.6 mm3 . The highest TGI (44.99 %) was registered in the group receiving a combination of 5 fluorouracil and XAV 939.Conclusion. The study revealed the ability of combined XAV 939 Wnt signaling pathway inhibitor and 5 fluorouracil to inhibit the growth of subcutaneous xenografts derived from patients with colorectal cancer.

Aim. To create heterotopic and orthotopic patient-derived xenograft (PDX) models of colorectal cancer (CRC) by transplantation of patient’s tumor samples into immunodeficient BALB / c Nude mice.Materials and methods. The study was performed on 15 female BALB / c Nude mice aged 6–8 weeks weighing 21–25 g. All animals underwent transplantation of the tumor material obtained from CRC patients into the following sites: heterotopic transplantation (under the skin of the thigh and into the omentum), orthotopic transplantation (into the descending and ascending colon and into the cecum). Weight and general condition of the animals and the size of the tumor nodule had been monitored for 80 days. The success of each model was assessed by the degree of engraftment, the dynamics of tumor growth, and the reproducibility of histopathologic characteristics. At the end of the experiment, the animals were euthanized by cervical dislocation.Results. 100% survival of the animals and similar tumor growth dynamics in the xenograft models were observed throughout the experiment. The analysis of histologic specimens obtained from the xenografts and patient’s tumor showed their correspondence to moderately differentiated intestinal adenocarcinoma. The main advantages and disadvantages of different variants of PDX models were described.Conclusion. Heterotopic and orthotopic PDX models reproduce the morpho-histologic characteristics of human tumors and demonstrate stable growth dynamics. Therefore, they are a suitable tool for the development, testing, and validation of potential anticancer drugs.

Purpose of the study. Was to reveal the antitumor effect of 2‑(6,8‑dimethyl‑5‑nitro‑4‑chloroquinoline‑2‑yl)‑5,6,7‑trichloro‑1,3‑tropolone in subcutaneous PDX models of human lung cancer.Material and methods. The studied tropolone was synthesized using a method of expanding the o‑quinone cycle. Assess to it’s toxic effects was given by the survival and changes in the health status of female Balb/c Nude mice. Antitumor tropolone effects were studied in subcutaneous patient‑derived xenograft (PDX) models of human squamous cell lung cancer in Balb/c Nude mice. The average volumes of tumor nodes and tumor growth inhibition (TGI %) rate were taken into account. Biochemical blood tests and histological analysis of the tumor material were performed in recipient mice.Results. An analysis of acute tropolone toxic effects did not reveal the lethal dose. The maximal TGI was observed on day 36 of the experiment in group 5 which have received 2.75 mg/g tropolone and accounted 73.5 % for females and 74.4 % for males. The average tumor volumes in females of this group were 431.3 ± 1,1 mm3 on day 33 of the experiment, in males – 428.9 ± 1,7 mm3 on day 30, and then the tumor volumes declined. The biochemical analysis of blood and histological examination of the tumor tissue of recipient mice reflect the severity of the antitumor effect on the dose of the studied tropolone.Conclusion. The research demonstrated the antitumor activity of 2‑(6,8‑dimethyl‑5‑nitro‑4‑chloroquinoline‑2‑yl)‑5,6,7‑trichloro‑1,3‑tropolone against subcutaneous PDX models of human NSCLC. The revealed tendencies can be used to search for effective modes of the compound application in clinical practice.