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Abstract Background Organoids are approved by the US FDA as an alternative to animal experiments to guide drug development and for sensitivity screening. Stable organoids models of gastric cancer are desirable for personalized medicine and drug screening. Methods Tumor tissues from a primary cancer of the stomach and metastatic cancer of the lymph node were collected for 3D culture. By long-term culture for over 50 generations in vitro, we obtained stably growing organoid lines. We analyzed short tandem repeats (STRs) and karyotypes of cancer cells, and tumorigenesis of the organoids in nude mice, as well as multi-omics profiles of the organoids. A CCK8 method was used to determine the drugs sensitivity to fluorouracil (5-Fu), platinum and paclitaxel. Results Paired organoid lines from primary cancer (SPDO1P) and metastatic lymph node (SPDO1LM) were established with unique STRs and karyotypes. The organoid lines resulted in tumorigenesis in vivo and had clear genetic profiles. Compared to SPDO1P from primary cancer, upregulated genes of SPDO1LM from the metastatic lymph node were enriched in pathways of epithelial-mesenchymal transition and angiogenesis with stronger abilities of cell migration, invasion, and pro-angiogenesis. Based on drug sensitivity analysis, the SOX regimen (5-Fu plus oxaliplatin) was used for chemotherapy with an optimal clinical outcome. Conclusions The organoid lines recapitulate the drug sensitivity of the parental tissues. The paired organoid lines present a step-change toward living biobanks for further translational usage.

Background: Organoids are approved by the US FDA as an alternative to animal experiments to guide drug development and for sensitivity screening. Stable organoids models of gastric cancer are desirable for personalized medicine and drug screening. Methods: Tumor tissues from a primary cancer of the stomach and metastatic cancer of the lymph node were collected for 3D culture. By long-term culture for over 50 generations in vitro, we obtained stably growing organoid lines. We analyzed short tandem repeats (STRs) and karyotypes of cancer cells, and tumorigenesis of the organoids in nude mice, as well as multi-omics profiles of the organoids. A CCK8 method was used to determine the drugs sensitivity to fluorouracil (5-Fu), platinum and paclitaxel. Results: Paired organoid lines from primary cancer (SPDO1P) and metastatic lymph node (SPDO1LM) were established with unique STRs and karyotypes. The organoid lines resulted in tumorigenesis in vivo and had clear genetic profiles. Compared to SPDO1P from primary cancer, upregulated genes of SPDO1LM from the metastatic lymph node were enriched in pathways of epithelial-mesenchymal transition and angiogenesis with stronger abilities of cell migration, invasion, and pro-angiogenesis. Based on drug sensitivity analysis, the SOX regimen (5-Fu plus oxaliplatin) was used for chemotherapy with an optimal clinical outcome. Conclusions: The organoid lines recapitulate the drug sensitivity of the parental tissues. The paired organoid lines present a step-change toward living biobanks for further translational usage. [ABSTRACT FROM AUTHOR]

Currently, colorectal cancer is still the third leading cause of cancer-related mortality, and the incidence is rising. It is a long time since the researchers used cancer cell lines and animals as the study subject. However, these models possess various limitations to reflect the cancer progression in the human body. Organoids have more clinical significance than cell lines, and they also bridge the gap between animal models and humans. Patient-derived organoids are three-dimensional cultures that simulate the tumor characteristics in vivo and recapitulate tumor cell heterogeneity. Therefore, the emergence of colorectal cancer organoids provides an unprecedented opportunity for colorectal cancer research. It retains the molecular and cellular composition of the original tumor and has a high degree of homology and complexity with patient tissues. Patient-derived colorectal cancer organoids, as personalized tumor organoids, can more accurately simulate colorectal cancer patients’ occurrence, development, metastasis, and predict drug response in colorectal cancer patients. Colorectal cancer organoids show great potential for application, especially preclinical drug screening and prediction of patient response to selected treatment options. Here, we reviewed the application of colorectal cancer organoids in disease model construction, basic biological research, organoid biobank construction, drug screening and personalized medicine, drug development, drug toxicity and safety, and regenerative medicine. In addition, we also displayed the current limitations and challenges of organoids and discussed the future development direction of organoids in combination with other technologies. Finally, we summarized and analyzed the current clinical trial research of organoids, especially the clinical trials of colorectal cancer organoids. We hoped to lay a solid foundation for organoids used in colorectal cancer research.

The emergence of organoids is considered a revolutionary model, changing the landscape of traditional translational research. These three-dimensional miniatures of human organs or tissues, cultivated from stem cells or biospecimens obtained from patients, faithfully replicate the structural and functional characteristics of specific target organs or tissues. In this extensive review, we explore the profound impact of organoids and assess the current state of living organoid biobanks, which are essential repositories for cryopreserving organoids derived from a variety of diseases. These resources hold significant value for translational research. We delve into the diverse origins of organoids, the underlying technologies, and their roles in recapitulating human development, disease modeling, as well as their potential applications in the pharmaceutical field. With a particular emphasis on biobanking organoids for prospective applications, we discuss how these advancements expedite the transition from bench to bedside translational research, thereby fostering personalized medicine and enriching our comprehension of human health.

Abstract Objective The use of novel methods to characterize living tumor cells relies on well-conceived biobanks. Herein, we raised the question of whether the composition of fresh and freeze/thawed dissociated tumor samples is comparable in terms of quantitative and qualitative profiling. Results Breast cancer is a heterogeneous disease, encompassing luminal A and B, basal/triple-negative breast cancer (TNBC), and ERBB2-like tumors. We examined living cells dissociated from TNBC and found that a classical freeze/thaw protocol leads to a marked reduction in the number of CD45−CD44LowCD24Low tumor cells. This, in turn, changed the percentage of tumor cells with certain CD44/CD24 expression patterns and changed the percentage of tumor-infiltrating immune cells. These cryopreservation-driven alterations in cellular phenotype make it impossible to compare fresh and frozen samples from the same patient directly. Moreover, the freeze/thaw process changed the transcriptomic signatures of triple-negative cancer stem cells in such a manner that hierarchical clustering no longer ranked them according to expected inter-individual differences. Overall, this study suggests that all analyses of living tumor cells should be conducted only using freshly dissociated tumors if we are to generate a robust scoring system for prognostic/predictive markers.

Biobanking plays an important role between clinical practice and translational research. In addition to the traditional biomolecular-based biobanks, there is a growing interest in establishing living biobanks, including organoid biobanks that can collect and store viable and functional tissues and proliferative cell types for long periods of time. An organoid is a three-dimensional cell complex derived by self-organization of small tissue blocks or stem cells, which can recapitulate the phenotypic and genetic characteristics of targeted human organs. Publications on brain organoids have increased recently, and several types of brain organoids have been reported to model normal and abnormal neural development, as well as different neurodegenerative diseases, neuropsychiatric disorders, and other neural conditions. Based on the current status of research, more exploration on brain organoids is needed, through technical advancements, to improve the reproducibility and scalability, as well as to decrease the diversity. Moreover, given their natural characteristics, more attention to ethical considerations is needed, considering the extent of maturation and complexity of brain organoids. Living biobanks that are engaged in collecting categories of brain organoids possessing different genetic backgrounds, and with spatial and temporal characteristics, will eventually contribute to the understanding of neural conditions and ultimately facilitate innovative treatment development. [ABSTRACT FROM AUTHOR]

Therapeutic approaches of advanced colorectal cancer are more complex, here we present a living biobank of patient-derived tumoroids from advanced colorectal cancer patients and show examples of how these tumoroids can be used to to simulate cancer behavior ex vivo and provide more evidence for tumoroids could be utilized as a predictive platform during chemotherapy treatment to identify the chemotherapy response. Morphological, histological and genomic characterization analysis of colorectal cancer tumoroids was conducted. Further, we treated colorectal cancer tumoroids with different drugs to detect cellular activities to evaluate drug sensitivity using CellTiter-Glo 3 D cell viability assay. Then the drug sensitivity of tumoroids was compared with clinical outcomes. Our results implied that tumoroids recapitulated the histological features of the original tumours and genotypic profiling of tumoroids showed a high-level of similarity to the matched primary tumours. Dose-response curves, area under the curve and tumour inhibitory rate of each therapeutic profiling calculations in tumoroids demonstrated a great diversity and we gained 88.24% match ratio between the sensitivity data of tumoroids with their paired patients' clinical outcomes. tumour inhibitory rate of each treatment parameters in tumoroids performed positive correlation with progression-free survival while area under the curve of each treatment parameters performed negative correlation with progression-free survival of the corresponding patients. In summary, We presented a living biobank of tumoroids from advanced colorectal cancer patients and show tumoroids got great potential for predicting clinical responses to chemotherapy treatment of advanced colorectal cancer.

Currently, colorectal cancer is still the third leading cause of cancer-related mortality, and the incidence is rising. It is a long time since the researchers used cancer cell lines and animals as the study subject. However, these models possess various limitations to reflect the cancer progression in the human body. Organoids have more clinical significance than cell lines, and they also bridge the gap between animal models and humans. Patient-derived organoids are three-dimensional cultures that simulate the tumor characteristics in vivo and recapitulate tumor cell heterogeneity. Therefore, the emergence of colorectal cancer organoids provides an unprecedented opportunity for colorectal cancer research. It retains the molecular and cellular composition of the original tumor and has a high degree of homology and complexity with patient tissues. Patient-derived colorectal cancer organoids, as personalized tumor organoids, can more accurately simulate colorectal cancer patients' occurrence, development, metastasis, and predict drug response in colorectal cancer patients. Colorectal cancer organoids show great potential for application, especially preclinical drug screening and prediction of patient response to selected treatment options. Here, we reviewed the application of colorectal cancer organoids in disease model construction, basic biological research, organoid biobank construction, drug screening and personalized medicine, drug development, drug toxicity and safety, and regenerative medicine. In addition, we also displayed the current limitations and challenges of organoids and discussed the future development direction of organoids in combination with other technologies. Finally, we summarized and analyzed the current clinical trial research of organoids, especially the clinical trials of colorectal cancer organoids. We hoped to lay a solid foundation for organoids used in colorectal cancer research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Luo, Ma, Zheng, Su and Huang.)

Simple Summary: Currently, organoid research is having a growing impact in oncology. Tumor organoids, directly derived from patients' specimens, can easily be expanded and cryopreserved. For that reason, they are becoming an indispensable ally in clinics for quicker diagnosis and prognosis of malignancies. Patient-derived cancer organoids are used as a platform to predict the efficacy of standard-of-care, as well as novel drugs. Therefore, this approach might be further utilized for validating off-label molecules, in order to widen the cancer care offer. Malignancies heterogeneity represents a critical issue in cancer care, as it often causes therapy resistance and tumor relapse. Organoids are three-dimensional (3D) miniaturized representations of selected tissues within a dish. Lately, organoid technology has been applied to oncology with growing success and Patients Derived Tumor Organoids (PDTOs) constitute a novel available tool which fastens cancer research. PDTOs are in vitro models of cancer, and importantly, they can be used as a platform to validate the efficacy of anti-cancer drugs. For that reason, they are currently utilized in clinics as emerging in vitro screening technology to tailor the therapy around the patient, with the final goal of beating cancer resistance and recurrence. In this sense, PDTOs biobanking is widely used and PDTO-libraries are helping the discovery of novel anticancer molecules. Moreover, they represent a good model to screen and validate compounds employed for other pathologies as off-label drugs potentially repurposed for the treatment of tumors. This will open up novel avenues of care thus ameliorating the life expectancy of cancer patients. This review discusses the present advancements in organoids research applied to oncology, with special attention to PDTOs and their translational potential, especially for anti-cancer drug testing, including off-label molecules. [ABSTRACT FROM AUTHOR]