Experimental Oncology Research Articles

Sonodynamic and sono-photodynamic therapy in oncology

In the present publication, authors have analyzed the results of using sonodynamic and sono-photodynamic therapy with photosensitizing agents of various classes (hematoporphyrin, 5-aminolevulinic acid, chlorin derivatives, etc.) in experimental oncology. In a number of in vitro and in vivo studies, the high antitumor efficacy of the above treatment methods has been proven. Ultrasonic treatment with a pulse frequency of 1–3 MHz and an intensity of 0.7 to 5 W/cm2 , independently and in combination with photo-irradiation of experimental tumors, can significantly improve the cytotoxic properties of photosensitizers. This became the basisfor testing the methodsin patients with malignant neoplasms of various localizations. Scientists fromSouth-East Asia presented the preliminary results of the use of sonodynamic and sono-photodynamic therapy with photosensitizers in the treatment of malignant pathology of the mammary gland, stomach, esophagus, prostate, lung and brain. Analysis of the obtained data indicates the absence of serious adverse events and an increase in the antitumor efficacy of treatment, which included these treatment methods with chlorin-type photosensitizers.

Analysis of Patent Activity in R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology of the NAS of Ukraine

Analysis of Patent Activity in R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology of the NAS of Ukraine

Аналіз патентної активності в Інституті експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України

Аналіз патентної активності в Інституті експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України

Testing monotherapy and combination therapy in one trial with biomarker consideration

It is a common scenario that an experimental oncology therapy, as a monotherapy, may be more effective than standard of care (SOC) in a biomarker positive population but less so or even inferior to SOC in biomarker negative population. At the same time, due to synergistic or additive effect, the combination of the two may be more effective than SOC alone in the all-comer population. The conventional development paradigm is to conduct two separate Phase III trials, one with the monotherapy versus SOC in the biomarker positive population, and the other with the combination therapy versus SOC in the all-comer population. In this manuscript, we propose a one-trial design that stratifies by biomarker status and randomizes biomarker positive patients into three arms (combination therapy, monotherapy, and SOC) and biomarker negative patients into two arms (combination therapy and SOC). There are two hypotheses in the proposed design and each addresses a different question. The family-wise type-I error rate (FWER) is smaller, due to shared control, than that of two separate trials. Therefore, no FWER adjustment is necessary in the proposed design and each hypothesis can be tested at the conventional 2.5% (one-sided) alpha level. The population for comparison between the combination therapy and SOC is skewed in the proposed design. A two-step log-rank statistic is proposed to account for the skewness. Power and sample size of the proposed design are evaluated in comparison with the two-trial paradigm. The proposed design is more efficient.

Factors Affecting Combination Trial Success (FACTS): Investigator Survey Results on Early-Phase Combination Trials.

Experimental therapeutic oncology agents are often combined to circumvent tumor resistance to individual agents. However, most combination trials fail to demonstrate sufficient safety and efficacy to advance to a later phase. This study collected survey data on phase 1 combination therapy trials identified from ClinicalTrials.gov between January 1, 2003 and November 30, 2017 to assess trial design and the progress of combinations toward regulatory approval. Online surveys (N = 289, 23 questions total) were emailed to Principal Investigators (PIs) of early-phase National Cancer Institute and/or industry trials; 263 emails (91%) were received and 113 surveys completed (43%). Among phase 1 combination trials, 24.9% (95%CI: 15.3%, 34.4%) progressed to phase 2 or further; 18.7% (95%CI: 5.90%, 31.4%) progressed to phase 3 or regulatory approval; and 12.4% (95%CI: 0.00%, 25.5%) achieved regulatory approval. Observations of “clinical promise” in phase 1 combination studies were associated with higher rates of advancement past each milestone toward regulatory approval (cumulative OR = 11.9; p = 0.0002). Phase 1 combination study designs were concordant with Clinical Trial Design Task Force (CTD-TF) Recommendations 79.6% of the time (95%CI: 72.2%, 87.1%). Most discordances occurred where no plausible pharmacokinetic or pharmacodynamic interactions were expected. Investigator-defined “clinical promise” of a combination is associated with progress toward regulatory approval. Although concordance between study designs of phase 1 combination trials and CTD-TF Recommendations was relatively high, it may be beneficial to raise awareness about the best study design to use when no plausible pharmacokinetic or pharmacodynamic interactions are expected.

<p>The impact of panitumumab treatment on survival and quality of life in patients with <em>RAS</em> wild-type metastatic colorectal cancer</p>

Panitumumab is a fully human monoclonal antibody targeting the epidermal growth factor receptor (EGFR). It is currently approved for the treatment of RAS wild-type (WT) metastatic colorectal cancer (mCRC) in combination with chemotherapy in first- and second-line and as monotherapy in chemorefractory patients. This review will provide an overview of main efficacy data on panitumumab from its early development up to latest evidences, including novel perspectives on predictive biomarkers of anti-EGFRs efficacy and mechanisms of secondary resistance. Quality of life (QoL) related issues and panitumumab safety profile will be addressed as well.

Erratum: Using Robotic Systems to Process and Embed Colonic Murine Samples for Histological Analyses.

An erratum was issued for: Using Robotic Systems to Process and Embed Colonic Murine Samples for Histological Analyses. An author affiliationwas updated. The affiliation for ClaudiaBurrello and Federica Facciotti was updated from: Department of Experimental Oncology, European Institute of Oncology to: Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS.

Ensuring radical surgery for liver malignancies

Despite significant progress in experimental oncology over the last few years, surgical approach is still gold standard in patients with different types of cancer including liver malignancies. Development of surgical techniques significantly improved immediate results of treatment. However, it should be noted that postoperative life expectancy is under much less attention in surgical practice. Different ways to achieve radical operations and improve long-term outcomes are reviewed in the article.

LITHIUM SALTS IN EXPERIMENTAL ONCOLOGY (REVIEW)

Recently, lithium salts have been considered as potential compounds for targeted therapy that can reduce tumor growth. There are a large number of publications indicating the effects of lithium on the signaling pathways used by tumor cells for growth and development, and have demonstrated that lithium can be used as antitumor agent in experimental oncology. The promise of using lithium salts to develop anticancer drugs is related to the fact that lithium has 2 main intracellular targets: glycogen synthase kinase-3β (GSK-3β) and inositol monophosphatase (IMPase), the inhibition of which by lithium can induce cancer cell death by apoptosis or autophagy. Lithium has been shown to block the proliferation of cancer cells by cell cycle arrest in the G2 /M phase, and also stimulates apoptosis and autophagy in cancer cells. This review summarizes data on the transport of lithium across cell membranes, characterizes its main intracellular targets and presents the results of studies in which lithium was used in experimental cancer therapy of various localization with an emphasis on signaling pathways used by cancer cells for growth and metastasis.

Гетерогенность и базальная аутофагия в клетках гепатокарциномы-29

The topic of research is the current direction of modern experimental oncology - the problem of studying the role of autophagy in the survival and death of a cancer cell. The purpose of this work was to study the cell heterogeneity of the hepatocarcinoma-29 population and the development of autophagy as a way of surviving tumor cells. The scientific significance of the work lies in obtaining previously unknown facts about the development of basal autophagy in certain types of hepatocarcinoma cells, which is a way of surviving tumor cells. The novelty of this study is to identify the types of hepatocarcinoma cells in which the process of autophagy develops, contributing to the survival of the tumor cell population and obtaining data on the structural features and activity of the autophagy process.The practical significance of the work lies in the possibility of using the obtained data for the development of targeted therapy of hepatocarcinoma through the combined use of inducers of autophagy and cytostatics, which will simultaneously use different cellular signaling pathways to stimulate apoptosis and autophagic cell death. The work was performed on the culture of hepatocarcinoma -29 cells using light and electron microscopy. The heterogeneity of the population of cells was revealed, which is determined by the size of the cells and the volume fraction of the nucleus and cytoplasm. In terms of cell volume and nuclear-cytoplasmic ratio, five types of cells are distinguished, corresponding to five stages of differentiation. In the IV and V cells of the differentiation stages, autophagic structures were revealed: autophagosomes, autolysosomes, and lysosomes. The findings make a significant contribution to cell biology, cytology and histology, as well as oncology. Key words: hepatocarcinoma-29, heterogeneity, stages of cell differentiation, autophag

The effect of lithium carbonate on the ultrastructural organization of cells of hepatocarcinoma-29 in the dynamics of cultivation

        The theme of the study is an actual direction of modern experimental Oncology – the problem of studying the influence of inducers of cell death on ultrastructural changes in tumor cells that contribute to the development of apoptosis. The aim of this work was to study the ultrastructural organization of hepatocarcinoma-29 cells under the influence of lithium carbonate in the dynamics of their cultivation.         The scientific significance and novelty of the work is to obtain new data on the ultrastructural organization of hepatocarcinoma cells under the influence of lithium carbonate. The novelty of this study is to identify consistent changes in the content and structure of cytoplasmic organelles of hepatocarcinoma-29 cells in the dynamics of cultivation with the introduction of lithium carbonate.          The practical significance of the work lies in the possibility of using the obtained data for the development of targeted therapy of hepatocarcinoma by the combined use of lithium carbonate and cytostatics, which will simultaneously involve various cellular signaling pathways for the stimulation of apoptosis and autophagic cell death. The work was performed on the culture of hepatocarcinoma cells -29 using light and electron microscopy.          Changes in the volume and numerical density of cytoplasmic organelles of G-29 cells in the dynamics of cultivation under the influence of lithium carbonate were revealed. It is shown that carbonate has a damaging effect on the cells of GA-29, which increases in the dynamics of cultivation. There is a decrease in the volume density of mitochondria, tanks of the granular endoplasmic network, free polysomal complexes, while increasing the volume density of autophagosomes, autolysosomes and lysosomes. The data obtained indicate that lithium carbonate contributes to the reduction of energy and synthetic functions of GA-29 cells, the development of catabolic processes in them and the launch of cell death processes.          The data obtained make a significant contribution to cell biology, Cytology and histology, as well as Oncology. The practical significance of the results is that on the basis of the identified ultrastructural changes in hepatocarcinoma cells under the influence of lithium carbonate, it is possible to develop approaches to targeted therapy of this type of cancer.           Key words: hepatocarcinoma-29, ultrastructure, lithium carbonate

The contribution of the Leningrad Scientific School to the formation of Russian experimental oncology in the first half of the XX century

The contribution of the Leningrad Scientific School to the formation of Russian experimental oncology in the first half of the XX century

Long-term effects after treatment with platinum compounds, cisplatin and [Pt(O,O′-acac)(γ-acac)(DMS)]: Autophagy activation in rat B50 neuroblastoma cells

Cisplatin (cisPt), among the best known components of multi-drug front-line therapies used for the treatments of solid tumors, such as the childhood neuroblastoma, acts through DNA linking. Nevertheless, the cisPt effectiveness is compromised by the onset of severe side effects, including neurotoxicity that results in neurodegeneration, cell death, and drug-resistance. In the field of experimental oncology, aimed at overcoming cytotoxicity and chemoresistance, great efforts are devoted to the synthesis of new platinum-based drugs, such as [Pt(O,O′-acac)(γ-acac)(DMS)] (PtAcacDMS), which shows a specific reactivity with sulfur residues of enzymes involved in apoptosis. Autophagy, an evolutionary conserved degradation pathway for recycling of cytoplasmic components, represents one of the mechanisms adopted by cancer cells which contribute to drug-resistance. In the present study, standard acute (48 h-exposure) and long-term effects (7 day-recovery after treatment or 7 day-recovery followed by reseeding and 96 h-growth), of cisPt and PtAcacDMS (40 and 10 μM, respectively) were investigated in vitro employing rat B50 neuroblastoma as a cancer model. Using fluorescence and electron microscopy, as well as biochemical techniques, our data highlight a key role of the autophagic process in B50 cells. Specifically, long-term effects caused by cisPt lead to inhibition of the apoptotic process and paralleled by the activation of autophagy, thus evidencing that autophagy has a protective role after cisPt exposure, allowing cells to survive. Whereas, long-term effects produced by PtAcacDMS lead toward both apoptosis and autophagy activation. In conclusion, autophagy may represents an alternative cell death pathway, circumventing drug-resistance strategies employed by cancer cells to survive chemoterapy.

Efficacy of Systemic Therapies for Relapsed/Refractory Indolent Non-Hodgkin Lymphoma (R/R iNHL): A Systematic Literature Review (SLR)

▪Introduction: Indolent non-Hodgkin lymphomas (iNHL), including follicular lymphoma (FL) and marginal zone lymphoma (MZL), are slow-growing lymphoid malignancies with high response rates to first-line treatment, but most patients (pts) will eventually relapse after initial response to treatment. For those with refractory disease (relapse ≤ 6 months after ending treatment), outcomes are worse. A number of treatment options based on chemo- and/or immunotherapy exist for pts with relapsed/refractory (R/R) iNHL, but currently there is no single standard treatment approach. There is a need to better understand the reported efficacy of available systemic treatments for R/R FL and MZL to guide treatment of iNHL.Methods: A SLR was carried out in accordance with PRISMA guidelines on September 1, 2017. Publications from MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and clinicaltrials.gov databases, as well as proceedings from the European Hematology Association and American Society of Clinical Oncology conferences held from 2015 to 2017, the International Conference on Malignant Lymphomas from 2013, 2015, and 2017, and from the American Society of Hematology, and European Society for Medical Oncology conferences from 2014 to 2016, were included. Studies were limited to articles published in English, sample sizes ≥ 40, and studies evaluating systemic therapy for adults with any-stage R/R FL, MZL, or mixed histologies with ≥ 70% R/R FL/MZL pts. Controlled or uncontrolled clinical trials and observational studies were included. Studies varied with respect to prior treatment received and pt response to prior treatment at enrollment. Pts were classified as relapsed, refractory, refractory to rituximab (R-refractory including double-refractory pts), R/R but sensitive or naïve to rituximab, or as general R/R if the type of relapse and/or refractoriness was not specified. Efficacy measures included overall response rate, complete response rate, progression-free survival (PFS), and duration of response (DoR). Relevant interventions included bendamustine (B) (alone or with rituximab [BR] or obinutuzumab [O+B]), idelalisib (ID), ibrutinib (IB), copanlisib (C), lenalidomide (L) (alone or with rituximab [R2]), R + cyclophosphamide + doxorubicin + vincristine + prednisone (R-CHOP), R + cyclophosphamide + vincristine + prednisone (R-CVP), and R + chlorambucil (R-Chl).Results: Of 58 publications identified representing 36 studies involving 3,759 pts: 1 study reported on R2, 2 on L, 5 on B, 6 on BR, 3 on ID, 3 on IB, 2 on C, 1 on O+B, 1 on R-CHOP, and 12 on R alone. After excluding studies that did not meet criteria for similarity, 19 studies reporting outcomes in iNHL pts were included. Six studies each reported on general R/R pts or R-refractory pts, 4 studies reported on pts with relapsed disease, and 2 studies each reported on pts with refractory disease or R-naïve/sensitive refractory disease. PFS in the general R/R population (n = 1,668) ranged from 4.4 months (mo) in pts treated with L to 17.9 mo in pts treated with BR. Only 1 study reported DoR for pts in the general R/R population. In relapsed pts, PFS was only reported or reached in 1 study (22.9 mo) and DoR ranged from 21.0 to 41.9 mo for BR. In R-refractory pts, PFS ranged from 9.3 mo in B-treated pts to 29.2 mo in O+B-treated pts. DoR ranged from 9.2 to 22.6 mo. BR was investigated in the widest variety of disease subsets (4) with PFS ranging from 17.9 mo in the general R/R population to 34.2 mo in the R-naïve/sensitive R/R population (Table). Outcomes are likely to have been influenced by pt and disease characteristics (e.g., relapsed vs refractory, rituximab sensitive vs refractory, FL International Prognostic Index risk) and response criteria used (Cheson 1999, Cheson 2007, Laboratory of Experimental Oncology and Radiobiology [LEXOR], or unknown).Conclusions: In pts with R/R iNHL (FL and MZL), there is significant variation in reported response and survival outcomes following systemic therapy. Currently, there is no clear standard of care for R/R iNHL, as demonstrated by the use of 9 different therapies across 19 studies identified in this SLR. Limited information is available on treatment outcomes for pts with different disease status and further studies are needed to determine the most appropriate treatment approach for specific subgroups of pts with R/R iNHL. [Display omitted] DisclosuresBachy:Roche: Honoraria; Beigene: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Takeda: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees. Fox:Celgene: Consultancy, Other: travel support, Speakers Bureau; Roche: Consultancy, Other: travel support, Research Funding, Speakers Bureau; Gilead: Consultancy, Other: travel support, Research Funding, Speakers Bureau; Janssen: Consultancy, Other: travel support, Speakers Bureau; Abbvie: Consultancy, Other: travel support, Research Funding, Speakers Bureau; Sunesis: Consultancy. Howlett:Celgene: Employment, Equity Ownership. Snedecor:Celgene: Research Funding. Franek:Celgene Corp.: Consultancy. Zaidi:Celgene Corp.: Consultancy. Tabah:Celgene Corporation: Employment.

From 3D spheroids to tumor bearing mice: efficacy and distribution studies of trastuzumab-docetaxel immunoliposome in breast cancer.

PurposeNanoparticles are of rising interest in cancer research, but in vitro canonical cell monolayer models are not suitable to evaluate their efficacy when prototyping candidates. Here, we developed three-dimensional (3D) spheroid models to test the efficacy of trastuzumab-docetaxel immunoliposomes in breast cancer prior to further testing them in vivo.Materials and methodsImmunoliposomes were synthesized using the standard thin film method and maleimide linker. Two human breast cancer cell lines varying in Her2 expression were tested: Her2+ cells derived from metastatic site: mammary breast MDA-MB-453 and triple-negative MDA-MB-231 cells. 3D spheroids were developed and tested with fluorescence detection to evaluate viability. In vivo efficacy and biodistribution studies were performed on xenograft bearing nude mice using fluorescent and bioluminescent imaging.ResultsIn vitro, antiproliferative efficacy was dependent upon cell type, size of the spheroids, and treatment scheduling, resulting in subsequent changes between tested conditions and in vivo results. Immunoliposomes performed better than free docetaxel + free trastuzumab and ado-trastuzumab emtansine (T-DM1). On MDA-MB-453 and MDA-MB-231 cell growth was reduced by 76% and 25%, when compared to free docetaxel + free trastuzumab and by 85% and 70% when compared to T-DM1, respectively. In vivo studies showed tumor accumulation ranging from 3% up to 15% of the total administered dose in MDA-MB-453 and MDA-MB-231 bearing mice. When compared to free docetaxel + free trastuzumab, tumor growth was reduced by 89% (MDA-MB-453) and 25% (MDA-MB-231) and reduced by 66% (MDA-MB-453) and 29% (MDA-MB-231) when compared to T-DM1, an observation in line with data collected from 3D spheroids experiments.ConclusionWe demonstrated the predictivity of 3D in vitro models when developing and testing nanoparticles in experimental oncology. In vitro and in vivo data showed efficient drug delivery with higher efficacy and prolonged survival with immunoliposomes when compared to current anti-Her2 breast cancer strategies.

Non-aversive photographic measurement method for subcutaneous tumours in nude mice.

We have developed a new method for the measurement of subcutaneous tumour volume which consists in taking photographs of mice in their home cages, to refine the standard method of measurement with calipers. We consider this new method to be non-aversive, as it may be more compatible with mice behavioural preferences and, therefore, improve their welfare. Photographs are captured when mice voluntarily go into an acrylic tube containing graph paper that is later used as a scale. Tumour volumes measured with the caliper and the non-aversive photographic method were compared to those obtained by water displacement volume and weight. Behavioural and physiological changes were evaluated to assess animal welfare. Significant differences were found between measurements obtained with the caliper and the non-aversive photographic method, v. the reference volume acquired by water displacement (P < 0.001). Nevertheless, there was good consistency for these measurements when tumours were measured repeatedly, with all Intra-Class Correlation Coefficients above 0.95. Mice on which the non-aversive photographic method was employed were significantly less reluctant to establish contact with the experimenter (P < 0.001) and behaved less anxiously in a modified-Novelty Suppressed Feeding test. Particularly, statistically significant differences were found in connection with the latency to eat an almond piece (P < 0.05), the frequency of grooming (P < 0.001) and the frequency of defecation (P < 0.001). Corticosterone concentration in faeces and blood glucose were determined and no significant changes were found. Therefore, we propose the non-aversive photographic method to measure subcutaneous tumours as a way to refine methodologies in the field of experimental oncology.

Abstract 4759: Designing clinical trials in tumor indications with a positive signal in phase 1

Abstract Increasingly, the conventional proof-of-concept randomized Phase 2 study is skipped in favor of directly going to Phase 3 after an experimental oncology drug has demonstrated promising anti-tumor activity in Phase 1 with a small sample size. This shift in the balance between certainty and speed is especially evident in the immune-oncology space where the tremendous success of immune checkpoint inhibitors has brought unprecedented competition in the field. The aggressive approach can be very risky no matter how promising an experimental drug appears in Phase 1. In this presentation, we introduce a novel adaptive design that mitigates the risk of late-stage programs. The proposed approach starts with a Phase 2 trial and adds an option in the design that allows the expansion of the Phase 2 trial into Phase 3 if the interim result based on the Phase 2 endpoint is promising. If the decision is to not expand, the study is kept as a Phase 2 trial and the primary analysis is conducted at the end of Phase 2. Otherwise, the study is expanded into a Phase 3 trial and the primary analysis of the study is conducted at the end of Phase 3, utilizing data from all enrolled patients including those already used for the decision making in the ongoing trial. The proposed approach is more efficient than the conventional approach that conducts and analyzes Phase 2 and Phase 3 trials sequentially, and is less risky than the contemporary approach of skipping Phase 2. Importantly, we will show that this design controls overall Type I error regardless of the expansion criterion. As a result, the study can still be considered positive even without expansion to Phase 3. Citation Format: Cong Chen, Keaven Anderson, Devan V. Mehrotra, Eric H. Rubin, Archie Tse. Designing clinical trials in tumor indications with a positive signal in phase 1 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4759.

MATERIALS OF SYMPOSIUM AND SUMMER SCHOOL “FUNDAMENTAL PRINCIPLES OF CANCER BIOTHERAPY”, MAY 21–23, 2018, KYIV, UKRAINE

The International Scientific Symposium “Fundamental Principles of Cancer Biotherapy” was held on May 21–23, 2018 in Kyiv, Ukraine. It was organized by R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology (IEPOR) of the National Academy of Sciences of Ukraine (NASU). The symposium was supported by the VACTRAIN project (TWINNING on DNA­based Cancer Vaccines, No 692293) in the frame of the European Union’s Horizon 2020 Research and Innovation Program.

Phosphorus-containing isothiocyanate-derived mercapturic acids as a useful alternative for parental isothiocyanates in experimental oncology

A series of phosphonates, phosphinates and phosphine oxides isothiocyanate-derived mercapturic acids were synthesized. A temperature dependence dynamic proton decoupled 31P NMR studies indicated that in most cases the compounds were obtained as a mixture of rotamers. Moreover, biologically relevant reversibility of mercapturic acids synthesis from the parental isothiocyanates was confirmed. All compounds were evaluated ashighly active antiproliferative agents in vitro in human colon cancer cell lines (LoVo and its doxorubicin-resistant subline LoVo/DX). The cell cycle progression and caspase-3 activity analyses revealed compounds moderate activity as apoptosis inducers and their poor influence on cell cycle progression in the LoVo cells. Our results confirm that isothiocyanate-derived mercapturic acids present a reasonable alternative for the parental compounds, and can replace them in the future studies on isothiocyanates potential as anticancer agents.

Organism-Level Tumor Models in Zebrafish Danio rerio

Development and implementation of adequate organism-level models is one of the key elements in biomedical research that focuses on experimental oncology. Over the last decade, studies using Zebrafish (Danio rerio) have gained in popularity in this area of research. This review describes the various approaches that have been used in developing highly effective models for oncological (clinical term, better cancer or tumor) studies based on D. rerio. Priority is given to transplantation models of cancer and their application to optically transparent D. rerio lines, including clonal ones, and utilization tumors of various origins bearing fluorescent labels. The combination of tumor transplantation at organism-level models in transparent clonal D. rerio lines with fluorescent microscopy, FACS-fractionation of tumor cell subsets, and transcription analysis can result in one of the most promising research approaches in providing new information on tumor formation and growth.