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Workflow of organoid vascularization. Implantation of tumoroids into highly vascularized tissues in animals is an effective approach for organoid vascularization. After organoids are engrafted in vasculature-rich mouse tissue, the host vasculature infiltrates the organoids. Another approach to generate vascularized organoids is combining the coculture of mixed cells or microfluidic platforms
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Cancer is a top-ranked life-threatening disease with intratumor heterogeneity. Tumor heterogeneity is associated with metastasis, relapse, and therapy resistance. These factors contribute to treatment failure and an unfavorable prognosis. Personalized tumor models faithfully capturing the tumor heterogeneity of individual patients are urgently need...
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Parkinson's disease (PD) is the second most common neurodegenerative disorder worldwide and is caused by the degeneration and loss of dopamine (DA) neurons in the ventral midbrain (VM). The focal and progressive degeneration of DA neurons in the VM makes PD a particularly attractive target for cell‐based therapies. Human pluripotent stem cells (hPS...
Citations
... In tumor research, organoids offer a robust model capable of being cultured, passaged, cryopreserved, and revived over extended periods. They maintain structural and functional similarity to the original tissue [6]. Unlike traditional two-dimensional (2D) cultures and patient-derived xenografts (PDX), tumor organoids demonstrate a notably higher success rate in construction. ...
Renal cell carcinoma, a leading cause of death in urological malignancies, arises from the nephron. Its characteristics include diversity in disease biology, varied clinical behaviors, different prognoses, and diverse responses to systemic therapies. The term ‘organoids’ is used to describe structures resembling tissues created through the three-dimensional cultivation of stem cells in vitro. These organoids, when derived from tumor tissues, can retain the diversity of the primary tumor, mirror its spatial tissue structure, and replicate similar organ-like functions. In contrast to conventional two-dimensional cell cultures and the transplantation of tumor tissues into other organisms, organoids derived from tumors maintain the complexity and microenvironment of the original tumor tissue. This fidelity makes them a more reliable model for the development of cancer drugs, potentially accelerating the translation of these drugs to clinical use and facilitating personalized treatment options for patients. This review aims to summarize the recent advancements in the use of organoids for studying renal cell carcinoma, focusing on their cultivation, potential applications, and inherent limitations.
... Tumor organoids play an essential role in translating basic research into novel therapeutic options for patients with cancer and serve as a prospective model for the study of cancer [29]. Patient-derived tumor tissue-based organoids can also be utilized to create customized treatment programs and precision drug efficacy assays [30]. In this investigation, we further established PDOs and elucidated a synergistic effect of the combination treatment of LIN and ATT on BC PDOs growth, providing the preclinical data of LIN and ATT combination for BC therapy. ...
... 221 Co-culturing tumor organoids with immune cells can simulate the TME (Figure 12(c)); the establishment of the PDO system using ALI, and the mock immune checkpoint blockade with anti-PD-1/anti-PD-L1 have been extensively reviewed elsewhere. 62,218 Moreover, Teijeira et al. 222 have tested the therapeutic efficacy of CEA-CD3 T-cell engagers on colon cancer by co-cultivating tumor organoids, autologous fibroblasts, and T cells. However, additional PDO methods have been established, including primary tumor-derived organotypic cell clusters for evaluating cancer immunotherapy, 223 a microfluidic perfusion system (EVIDENT) for studying the interaction between tumor fragments and TILs, 224 and a microfluidic chip device developed by Haque et al. 225 to simulate the PDAC TME and observe the active crosstalk between cancer and stromal cells. ...
... Adapted from Cattaneo et al.217 (c) Tumor organoids were co-cultured with immune cells to construct the immune microenvironment. Adapted from Xu et al.218 (d) Retained fibroblasts in human and mouse tumor organoids. ...
Digestive system tumors are the leading cause of cancer-related deaths worldwide. Despite ongoing research, our understanding of their mechanisms and treatment remain inadequate. One promising tool for clinical applications is the use of gastrointestinal tract tumor organoids, which serve as an important in vitro model. Tumor organoids exhibit a genotype similar to the patient’s tumor and effectively mimic various biological processes, including tissue renewal, stem cell, and ecological niche functions, and tissue response to drugs, mutations, or injury. As such, they are valuable for drug screening, developing novel drugs, assessing patient outcomes, and supporting immunotherapy. In addition, innovative materials and techniques can be used to optimize tumor organoid culture systems. Several applications of digestive system tumor organoids have been described and have shown promising results in related aspects. In this review, we discuss the current progress, limitations, and prospects of this model for digestive system tumors.
... In 2018 Vlachogiannis and colleagues described for the first time that drug responses in PDOs recapitulate patient responses to chemotherapy or novel agents with 93% specificity and 100% sensitivity (43). To date, different investigations have highlighted the consistent prediction of treatment responses across organoids, and corresponding tumors (44). For example, Tiriac et al. conducted a study where they identified molecular signatures associated with favorable responses to treatments in organoids of pancreatic cancers. ...
A key challenge in cancer research is the meticulous development of models that faithfully emulates the intricacies of the patient scenario, with emphasis on preserving intra-tumoral heterogeneity and the dynamic milieu of the tumor microenvironment (TME). Organoids emerge as promising tool in new drug development, drug screening and precision medicine. Despite advances in the diagnoses and treatment of pediatric cancers, certain tumor subtypes persist in yielding unfavorable prognoses. Moreover, the prognosis for a significant portion of children experiencing disease relapse is dismal. To improve pediatric outcome many groups are focusing on the development of precision medicine approach. In this review, we summarize the current knowledge about using organoid system as model in preclinical and clinical solid-pediatric cancer. Since organoids retain the pivotal characteristics of primary parent tumors, they exert great potential in discovering novel tumor biomarkers, exploring drug-resistance mechanism and predicting tumor responses to chemotherapy, targeted therapy and immunotherapies. We also examine both the potential opportunities and existing challenges inherent organoids, hoping to point out the direction for future organoid development.
... Поэтому неудивительно, что на сегодняшний день органоидные культуры получены из многих типов опухолей, таких как рак легкого, молочной железы, печени и др. [16]. При этом частота успешного создания долгосрочных органоидных культур из опухолей предстательной железы значительно ниже, чем для многих других опухолей [17]. ...
Background. Analyzing the sensitivity of patient-derived tumor organoids to anti-cancer medications shows great potential for tailoring personalized treatment plans.
Aim. To obtain two prostate tumor organoid cultures, optimize the composition of culture medium, and to evaluate
the efficacy of the chemotherapeutic drug docetaxel using the obtained organoid cultures.
Materials and methods. The initial tissue was dissociated using the gentleMACS Octo homogenizer. The obtained cells were cultured in Matrigel with different culture media for selection of the optimal one. Cell viability and growth rates were assessed using the MTS assay.
Results. In this study, we successfully obtained two organoid cultures of prostate cancer cells and identified the most effective composition of culture medium. Using a cytotoxic test, it was shown that the obtained organoid cultures of prostate cancer cells had different sensitivity to docetaxel which was reflected in different inhibition of the tumor cell growth rate.
Conclusion. The utilization of prostate cancer organoids to determine the best treatment approach is a highly promising experimental technology. Nevertheless, additional research is required before integration of this technology into clinical practice.
... 21,22 High tumor heterogeneity is associated with more aggressive behavior, worse response to treatment, and worse prognosis, which poses a major challenge for personalized medicine. 23,24 In recent years, the assessment of intratumoral heterogeneity using 18 F-FDG PET scanning with various parameters has gained increasing attention. Several approaches have been proposed to study tumor heterogeneity using 18 F-FDG PET/CT, among which texture analysis has been widely applied. ...
Background
The aim of the present study was to evaluate the impact of intratumoral metabolic heterogeneity and quantitative ¹⁸F‐FDG PET/CT imaging parameters in predicting patient outcomes in thymic epithelial tumors (TETs).
Methods
This retrospective study included 100 patients diagnosed with TETs who underwent pretreatment ¹⁸F‐FDG PET/CT. The maximum and mean standardized uptake values (SUVmax and SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) on PET/CT were measured. Heterogeneity index‐1 (HI‐1; standard deviation [SD] divided by SUVmean) and heterogeneity index‐2 (HI‐2; linear regression slopes of the MTV according with different SUV thresholds), were evaluated as heterogeneity indices. Associations between these parameters and patient survival outcomes were analyzed.
Results
The univariate analysis showed that Masaoka stage, TNM stage, WHO classification, SUVmax, SUVmean, TLG, and HI‐1 were significant prognostic factors for progression‐free survival (PFS), while MTV, HI‐2, age, gender, presence of myasthenia gravis, and maximum tumor diameter were not. Subsequently, multivariate analyses showed that HI‐1 (p < 0.001) and TNM stage (p = 0.002) were independent prognostic factors for PFS. For the overall survival analysis, TNM stage, WHO classification, SUVmax, and HI‐1 were significant prognostic factors in the univariate analysis, while TNM stage remained an independent prognostic factor in multivariate analyses (p = 0.024). The Kaplan Meier survival analyses showed worse prognoses for patients with TNM stages III and IV and HI‐1 ≥ 0.16 compared to those with stages I and II and HI‐1 < 0.16 (log‐rank p < 0.001).
Conclusion
HI‐1 and TNM stage were independent prognostic factors for progression‐free survival in TETs. HI‐1 generated from baseline ¹⁸F‐FDG PET/CT might be promising to identify patients with poor prognosis.
... It is crucial to optimize the balance between the quantity of cancer cells and mesoscale collagen bundles in order to achieve optimal outcomes. PDTO possess the capability to facilitate the advancement of personalized therapeutic approaches for cancer patients [16,22,49,50]. In our investigations, lung cancer organoids cultured in MC-gel accurately recapitulate the histological characteristics and mutational profile of the original tumor from the donor patient. ...
Patient-derived tumor organoids (PDTOs) shows great potential as a preclinical model. However, the current methods for establishing PDTOs primarily focus on modulating local properties, such as sub-micrometer topographies. Nevertheless, they neglect to capture the global millimeter or intermediate mesoscale architecture that have been demonstrated to influence tumor response to therapeutic treatment and tumor progression. In this study, we present a rapid technique for generating collagen bundles with an average length of 90 ± 27 μm and a mean diameter of 5 ± 1.5 μm from tumor tissue debris that underwent mechanical agitation following enzymatic digestion. The collagen bundles were subsequently utilized for the fabrication of biomimetic hydrogels, incorporating microbial transglutaminase (mTG) crosslinked gelatin. These biomimetic hydrogels, referred to as MC-gel, were specifically designed for patient-derived tumor organoids. The lung cancer organoids cultured in MC-gel exhibited larger diameters and higher cell viability compared to those cultured in gels lacking the mesoscale collagen bundle; moreover, their irregular morphology more closely resembled that observed in vivo. The MC-gel-based lung cancer organoids effectively replicated the histology and mutational landscapes observed in the original donor patient’s tumor tissue. Additionally, these lung cancer organoids showed a remarkable similarity in their gene expression and drug response across different matrices. This recently developed model holds great potential for investigating the occurrence, progression, metastasis, and management of tumors, thereby offering opportunities for personalized medicine and customized treatment options.
... In recent years, the application of personalized treatments based on genetic information has been initiated in the field of cancer medicine [1]. Generally, genetic information is obtained from surgically resected cancerous tissues [2,3]. ...
Background: The application of personalized cancer treatment based on genetic information and surgical samples has begun in the field of cancer medicine. However, a biopsy may be painful for patients with advanced diseases that do not qualify for surgical resection. Patient-derived xenografts (PDXs) are cancer models in which patient samples are transplanted into immunodeficient mice. PDXs are expected to be useful for personalized medicine. The aim of this study was to establish a PDX from body fluid (PDX-BF), such as peritoneal and pleural effusion samples, to provide personalized medicine without surgery. Methods: PDXs-BF were created from patients with ovarian cancer who had positive cytology findings based on peritoneal and pleural effusion samples. PDXs were also prepared from each primary tumor. The pathological findings based on immunohistochemistry were compared between the primary tumor, PDX, and PDX-BF. Further, genomic profiles and gene expression were evaluated using DNA and RNA sequencing to compare primary tumors, PDXs, and PDX-BF. Results: Among the 15 patients, PDX-BF was established for 8 patients (5 high-grade serous carcinoma, 1 carcinosarcoma, 1 low-grade serous carcinoma, and 1 clear cell carcinoma); the success rate was 53%. Histologically, PDXs-BF have features similar to those of primary tumors and PDXs. In particular, PDXs-BF had similar gene mutations and expression patterns to primary tumors and PDXs. Conclusions: PDX-BF reproduced primary tumors in terms of pathological features and genomic profiles, including gene mutation and expression. Thus, PDX-BF may be a potential alternative to surgical resection for patients with advanced disease.
... Up to date, multiple groups reported the generation of gastric PDOs in their own way, which were obtained from diverse sources including surgical resection specimens, endoscopic biopsy, etc. One major challenge in cancer organoid culture is the purity of tumor cells (36). Tumor biopsy always has normal cell contamination, and the overgrowth of normal cells can affect the growth of cancerous cells. ...
... cancer that organoids are a suitable system for testing in vitro sensitivity to different kinds of compounds and simulateing therapeutics efficiency for clinical applications since organoid keep the characteristics of organ of origin (36). The most advantageous feature of organoid-based drug screening is that the test utilizes organoid directed from patient, so it can reflect characteristics of individual patient. ...
The elucidation of the pathophysiology underlying various diseases necessitates the development of research platforms that faithfully mimic in vivo conditions. Traditional model systems such as two-dimensional cell cultures and animal models have proven inadequate in capturing the complexities of human disease modeling. However, recent strides in organoid culture systems have opened up new avenues for comprehending gastric stem cell homeostasis and associated diseases, notably gastric cancer. Given the significance of gastric cancer, a thorough understanding of its pathophysiology and molecular underpinnings is imperative. To this end, the utilization of patient-derived organoid libraries emerges as a remarkable platform, as it faithfully mirrors patient-specific characteristics, including mutation profiles and drug sensitivities. Furthermore, genetic manipulation of gastric organoids facilitates the exploration of molecular mechanisms underlying gastric cancer development. This review provides a comprehensive overview of recent advancements in various adult stem cell-derived gastric organoid models and their diverse applications.
... Tumoroids mimic the primary tissue in both architecture and function and retain the histopathological features, genetic profile, mutational landscape, and even responses to therapy. 34 The use of tumoroids is expanding, and their utility for basic research and early steps of drug development has been recognized. 35 Cisplatin, for example, has been found to be less effective in patient-derived organoids (PDOs) generated from non-small cell lung cancer (NSCLC) tissues than from cell lines, highlighting the ability of patient-derived material to provide important information on potential resistance mechanisms. ...
Cancer, a complex and multifactorial disease, presents a significant challenge to global health. Despite significant advances in surgical, radiotherapeutic and immunological approaches, which have improved cancer treatment outcomes, drug therapy continues to serve as a key therapeutic strategy. However, the clinical efficacy of drug therapy is often constrained by drug resistance and severe toxic side effects, and thus there remains a critical need to develop novel cancer therapeutics. One promising strategy that has received widespread attention in recent years is drug repurposing: the identification of new applications for existing, clinically approved drugs. Drug repurposing possesses several inherent advantages in the context of cancer treatment since repurposed drugs are typically cost-effective, proven to be safe, and can significantly expedite the drug development process due to their already established safety profiles. In light of this, the present review offers a comprehensive overview of the various methods employed in drug repurposing, specifically focusing on the repurposing of drugs to treat cancer. We describe the antitumor properties of candidate drugs, and discuss in detail how they target both the hallmarks of cancer in tumor cells and the surrounding tumor microenvironment. In addition, we examine the innovative strategy of integrating drug repurposing with nanotechnology to enhance topical drug delivery. We also emphasize the critical role that repurposed drugs can play when used as part of a combination therapy regimen. To conclude, we outline the challenges associated with repurposing drugs and consider the future prospects of these repurposed drugs transitioning into clinical application. Signal Transduction and Targeted Therapy (2024) 9:92 ; https://doi.
