The future of tumor organoids in precision therapy

Trends in cancer, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Tumoroids are cultures of patient-derived tumor cells, which grown in 3D the presence an extracellular matrix extract and specific growth factors. can be generated from adult as well pediatric cancers, including epithelial sarcomas, brain cancers. retain multi-omic characteristics their corresponding recapitulate interpatient intratumor heterogeneity. Retrospective prospective studies have demonstrated that tumoroids predict patient responses to anticancer therapies, making them a promising tool for precision oncology. However, several challenges remain before fully integrated into clinical decision-making, success rates tumoroid establishment turnaround times. This review discusses current advances, challenges, future directions tumoroid-based models cancer research therapy.

Language: Английский

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Establishment of patient-derived 3D in vitro models of sarcomas: literature review and guidelines on behalf of the FORTRESS working group

Neoplasia, Journal Year: 2025, Volume and Issue: 65, P. 101171 - 101171

Published: May 3, 2025

Language: Английский

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Bridging the gap: advancing cancer cell culture to reveal key metabolic targets

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: Sept. 17, 2024

Metabolic rewiring is a defining characteristic of cancer cells, driving their ability to proliferate. Leveraging these metabolic vulnerabilities for therapeutic purposes has long and impactful history, with the advent antimetabolites marking significant breakthrough in treatment. Despite this, only few vitro discoveries have been successfully translated into effective clinical therapies. This limited translatability partially due use simplistic models that do not accurately reflect tumor microenvironment. Review examines effects current cell culture practices on metabolism highlights recent advancements establishing more physiologically relevant conditions technologies, such as organoids. Applying improvements may bridge gap between vivo findings, facilitating development innovative therapies cancer.

Language: Английский

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Approaches for studying neuroimmune interactions in Alzheimer’s disease

Trends in Immunology, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 1, 2024

Language: Английский

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Recapitulating the tumor microenvironment in a dish, one cell type at a time

Cell Reports Methods, Journal Year: 2024, Volume and Issue: 4(6), P. 100800 - 100800

Published: June 1, 2024

The tumor microenvironment harbors a variety of different cell types that differentially impact biology. In this issue Cell Reports Methods, Raffo-Romero et al. standardized and optimized 3D organoids to model the interactions between tumor-associated macrophages cells in vitro. Tumors are complex ecosystems contain many exhibiting diverse functional states. Importantly, non-tumoral (TME) facets biology, including angiogenesis, migration metastasis, anti-tumor immunity.1de Visser K.E. Joyce J.A. evolving microenvironment: From cancer initiation metastatic outgrowth.Cancer Cell. 2023; 41: 374-403https://doi.org/10.1016/j.ccell.2023.02.016Abstract Full Text PDF PubMed Scopus (382) Google Scholar complexity TME vivo limits conclusions can be drawn from vitro models progression therapy response. addition, oftentimes cannot propagated as 2D cultures vitro, thereby limiting application these an individual patient's ex vivo. To overcome several limitations, organoid have been developed recent years substantially expand use models, propagation previously hard-to-propagate cancers, enabling more physiological modeling tumor-matrix faithful recapitulation spatial organization tumors.2Drost J. Clevers H. Organoids research.Nat. Rev. Cancer. 2018; 18: 407-418https://doi.org/10.1038/s41568-018-0007-6Crossref (1055) Despite advances, still do not recapitulate Most importantly, conventional mainly while lacking make up TME. This represents important limitation for prediction responses, since exert major on efficacy therapies. As one example, (TAMs), which among most abundant types, play role modulating responses immunotherapy chemotherapy.3De Palma M. Lewis C.E. Macrophage Regulation Tumor Responses Anticancer Therapies.Cancer 2013; 23: 277-286https://doi.org/10.1016/j.ccr.2013.02.013Abstract (858) Scholar,4Duan Z. Luo Y. Targeting immunotherapy.Sig. Transduct. Target Ther. 2021; 6: 127https://doi.org/10.1038/s41392-021-00506-6Crossref (309) Several studies addressed either by devising autologous integrate stromal original or reconstituting with allogeneic exogenous other sites, such peripheral blood.5LeSavage B.L. Suhar R.A. Broguiere N. Lutolf M.P. Heilshorn S.C. Next-generation organoids.Nat. Mater. 2022; 21: 143-159https://doi.org/10.1038/s41563-021-01057-5Crossref (173) Scholar,6Cattaneo C.M. Dijkstra K.K. Fanchi L.F. Kelderman S. Kaing van Rooij den Brink Schumacher T.N. Voest E.E. organoid–T-cell coculture systems.Nat. Protoc. 2020; 15: 15-39https://doi.org/10.1038/s41596-019-0232-9Crossref (185) These approaches exhibit advantages preserving composition providing easier manipulation expansion prior co-culture. Studies employing methods enabled immunotherapy7Neal J.T. Li X. Zhu Giangarra V. Grzeskowiak C.L. Ju Liu I.H. Chiou S.-H. Salahudeen A.A. Smith A.R. al.Organoid Modeling Immune Microenvironment.Cell. 175: 1972-1988.e16https://doi.org/10.1016/j.cell.2018.11.021Abstract (819) thus promise pave way toward responses. However, is their lack standardization. divergent optimal growth conditions rendering it necessary optimize culture combinations tumoral cells. al.8Raffo-Romero A. Chaouche L.Z. Salomé-Desnoulez Hajjaji Fournier I. Salzet Duhamel A co-culture system breast tumoroids study therapeutic responses.Cell Rep. Methods. 2024; 4: 100792https://doi.org/10.1016/j.crmeth.2024.100792Abstract address limitations three patient-derived macrophages. first step, authors protocol deriving blood monocytes systematically assessing detachment approaches. cryopreserved allows decoupling later synchronizing generation derived same patient. Next, established co-culturing organoids: semi-liquid two solid-state systems. preparation all co-cultures, were recovered Matrigel drops mixed dye-labeled at fixed ratio. approach, medium 2% Matrigel, facilitating direct interaction types. solid systems, embedded matrix together within (termed "inner co-culture") layered outside top "external co-culture"). then tracked localization over course days found aggregated around organoids. Notably, external infiltrated also interacted organoids, indicating approach may suitable infiltration TAMs. Not surprisingly, proportion was lower than setups, and, degree setups proved reproducible across experiments. next sought characterize systems using immunofluorescence light-sheet microscopy. substantial background noise conditions, integrated step clear formamide polyethylene glycol, accurate identification organoid-infiltrating It well adopt specific phenotypes after infiltrating TME.9Mantovani Allavena P. Marchesi F. Garlanda C. Macrophages tools targets therapy.Nat. Drug Discov. 799-820https://doi.org/10.1038/s41573-022-00520-5Crossref (495) assess recapitulated upon performed proteomic profiling comparing cultured alone co-cultured experiments revealed differential upregulation genes implicated pathways known highly expressed Thus, results indicate devised elicits gene expression programs upregulated TAMs Interestingly, phenotypic analysis prototypical anti-inflammatory "M2-like" markers flow cytometry subtle differences implementation imparts effects canonical TAM phenotypes. presence molecular profile end, they perform spatially resolved lipidomics grown show modulated lipid profiles enhanced signals ceramide lysophospholipid-related lipids. One clinically salient applications framework precision medicine.10Bose Shen Promises challenges organoid-guided medicine.Med. 2: 1011-1026https://doi.org/10.1016/j.medj.2021.08.005Abstract (60) Having cancer-macrophage finally chemotherapy response harnessed determined susceptibility paclitaxel, chemotherapeutic drug commonly used treatment cancer. absence susceptible paclitaxel-mediated toxicity. data recapitulates effect shielding paclitaxel-induced death.11Olson O.C. Kim Quail D.F. Foley E.A. Tumor-Associated Suppress Cytotoxic Activity Antimitotic Agents.Cell 2017; 19: 101-113https://doi.org/10.1016/j.celrep.2017.03.038Abstract (90) exploration highlights strengths depending question hand. While suited best imaging entire easily recovering assessments, better interrogation cell-matrix into More generally, illustrates benefit careful optimization standardization steps comprising intriguing envision future extensions protocols presented For target checkpoint immunotherapy.12Gordon S.R. Maute R.L. Dulken B.W. Hutter G. George B.M. McCracken M.N. Gupta R. Tsai J.M. Sinha Corey D. al.PD-1 tumour-associated inhibits phagocytosis tumour immunity.Nature. 545: 495-499https://doi.org/10.1038/nature22396Crossref (1455) Therefore, would insightful establish additional integration T dual applying similarly interesting directly compare monocyte-derived here Of note, possibility decoupled employed allow experimental perturbation both immune compartments. Overall, marks advance multiple readouts. lays out systematic designing optimizing work supported Max Eder grant German Cancer Aid (reference 70114327), Fritz Thyssen Foundation 10.24.1.010MN), fellowship Charité-BIH Digital Clinician Scientist Program. author declares no competing interests. responsesRaffo-Romero al.Cell MethodsJune 10, 2024In Brief3D replicate diversity but devise human tumoroids. By tracking macrophage-tumoroid interactions, influence response, emphasizing need enhance representation. Full-Text Open Access

Language: Английский

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The Use of Patient-Derived Organoids in the Study of Molecular Metabolic Adaptation in Breast Cancer

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(19), P. 10503 - 10503

Published: Sept. 29, 2024

Around 13% of women will likely develop breast cancer during their lifetime. Advances in metabolism research have identified a range metabolic reprogramming events, such as altered glucose and amino acid uptake, increased reliance on glycolysis, interactions with the tumor microenvironment (TME), all which present new opportunities for targeted therapies. However, studying these networks is challenging traditional 2D cell cultures, often fail to replicate three-dimensional architecture dynamic real tumors. To address this, organoid models emerged powerful tools. Tumor organoids are 3D derived from patient tissue, that more accurately mimic structural functional properties actual tissues vivo, offering realistic model investigating metabolism. This review explores unique adaptations discusses how can provide deeper insights into processes. We evaluate most advanced tools culture models, including optical imaging (OMI), matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MSI), recent advances conventional techniques applied cultures. Finally, we explore progress made identifying targeting potential therapeutic targets

Language: Английский

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Protocol for generating a co-culture of macrophages with breast cancer tumoroids

STAR Protocols, Journal Year: 2024, Volume and Issue: 6(1), P. 103536 - 103536

Published: Dec. 20, 2024

Language: Английский

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The new platform for cancer immunity research: Organoid systems

Elsevier eBooks, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Language: Английский

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