Orthotopic and metastatic tumour models in preclinical cancer research

Pharmacology & Therapeutics, Journal Year: 2024, Volume and Issue: 257, P. 108631 - 108631

Published: March 11, 2024

Mouse models of disease play a pivotal role at all stages cancer drug development. Cell-line derived subcutaneous tumour are predominant in early discovery, but there is growing recognition the importance more complex orthotopic and metastatic for understanding both target biology correct tissue context, impact microenvironment immune system responses to treatment. The aim this review highlight value that bring study development while pointing out those most likely be encountered literature. Important developments models, such as increasing use passage patient material (PDXs, organoids) humanised mouse discussed, these approaches have potential increase predictive preclinical studies, ultimately improve success rate anticancer drugs clinical trials.

Language: Английский

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Druggable growth dependencies and tumor evolution analysis in patient-derived organoids of neuroendocrine neoplasms from multiple body sites

Cancer Cell, Journal Year: 2023, Volume and Issue: 41(12), P. 2083 - 2099.e9

Published: Dec. 1, 2023

Neuroendocrine neoplasms (NENs) comprise well-differentiated neuroendocrine tumors (NETs) and poorly differentiated carcinomas (NECs). Treatment options for patients with NENs are limited, in part due to lack of accurate models. We establish patient-derived tumor organoids (PDTOs) from pulmonary NETs derive PDTOs an understudied subtype NEC, large cell carcinoma (LCNEC), arising multiple body sites. maintain the gene expression patterns, intra-tumoral heterogeneity, evolutionary processes parental tumors. Through hypothesis-driven drug sensitivity analyses, we identify ASCL1 as a potential biomarker response LCNEC treatment BCL-2 inhibitors. Additionally, discover dependency on EGF NET PDTOs. Consistent these findings, find that, independent cohort, approximately 50% express EGFR. This study identifies actionable vulnerability subset NETs, emphasizing utility PDTO

Language: Английский

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Integration of pan-omics technologies and three-dimensional in vitro tumor models: an approach toward drug discovery and precision medicine

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: March 9, 2024

Abstract Despite advancements in treatment protocols, cancer is one of the leading cause deaths worldwide. Therefore, there a need to identify newer and personalized therapeutic targets along with screening technologies combat cancer. With advent pan-omics technologies, such as genomics, transcriptomics, proteomics, metabolomics, lipidomics, scientific community has witnessed an improved molecular metabolomic understanding various diseases, including In addition, three-dimensional (3-D) disease models have been efficiently utilized for pathophysiology tools drug discovery. An integrated approach utilizing 3-D vitro tumor led intricate network encompassing signalling pathways cross-talk solid tumors. present review, we underscore current trends omics highlight their role genotypic-phenotypic co-relation respect models. We further discuss challenges associated provide our outlook on future applications these discovery precision medicine management Graphical

Language: Английский

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Patient-derived organoids in precision cancer medicine

Med, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 1, 2024

Language: Английский

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Epigenetic modifications in early stage lung cancer: pathogenesis, biomarkers, and early diagnosis

MedComm, Journal Year: 2025, Volume and Issue: 6(3)

Published: Feb. 21, 2025

Abstract The integration of liquid biopsy with epigenetic markers offers significant potential for early lung cancer detection and personalized treatment. Epigenetic alterations, including DNA methylation, histone modifications, noncoding RNA changes, often precede genetic mutations are critical in progression. In this study, we explore how biopsy, combined markers, can provide cancer, potentially predicting onset up to 4 years before clinical diagnosis. We discuss the challenges targeting regulators, which could disrupt cellular balance if overexploited, need maintaining key gene expressions therapeutic applications. This review highlights promise using early‐stage diagnosis, a focus on optimizing treatment strategies precision medicine.

Language: Английский

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Organoid: Bridging the gap between basic research and clinical practice

Cancer Letters, Journal Year: 2023, Volume and Issue: 572, P. 216353 - 216353

Published: Aug. 18, 2023

Language: Английский

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Toward reproducible tumor organoid culture: focusing on primary liver cancer

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: March 20, 2024

Organoids present substantial potential for pushing forward preclinical research and personalized medicine by accurately recapitulating tissue tumor heterogeneity in vitro . However, the lack of standardized protocols cancer organoid culture has hindered reproducibility. This paper comprehensively reviews current challenges associated with highlights recent multidisciplinary advancements field a specific focus on standardizing liver culture. We discuss non-standardized aspects, including sources, processing techniques, medium formulations, matrix materials, that contribute to technical variability. Furthermore, we emphasize need establish reproducible platforms preserve genetic, proteomic, morphological, pharmacotypic features parent tumor. At end each section, our shifts standardization primary cancer. By addressing these challenges, can enhance reproducibility clinical translation systems, enabling their applications precision medicine, drug screening, research.

Language: Английский

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Advancing cancer research through organoid technology

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: Nov. 8, 2024

The complexity of tumors and the challenges associated with treatment often stem from limitations existing models in accurately replicating authentic tumors. Recently, organoid technology has emerged as an innovative platform for tumor research. This bioengineering approach enables researchers to simulate, vitro, interactions between their microenvironment, thereby enhancing intricate interplay cells surroundings. Organoids also integrate multidimensional data, providing a novel paradigm understanding development progression while facilitating precision therapy. Furthermore, advancements imaging genetic editing techniques have significantly augmented potential organoids review explores application more precise simulations its specific contributions cancer research advancements. Additionally, we discuss evolving trends developing comprehensive utilizing technology.

Language: Английский

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A growth factor-reduced culture system for colorectal cancer organoids

Cancer Letters, Journal Year: 2024, Volume and Issue: 588, P. 216737 - 216737

Published: Feb. 19, 2024

Although organoids derived from tumor tissues have been widely used in cancer research, it is a great challenge for cultured to retain the characteristics of original due their heterogeneity. In this study, we explore organoid culture recipes capture features colorectal cancers. We find that activation Wnt and EGF signaling inhibition BMP are non-essential survival most (CRCOs). design growth factor-reduced medium containing FGF10, A83-01 (TGF-β type I receptor inhibitor), SB202190 (p38 MAPK gastrin, nicotinamide. Using medium, can maintain long-term CRCO cultivation, as evidenced by histopathology, genetic stability, tumorigenicity, response clinical treatments. Our findings offer reliable economical strategy culture, facilitating utilization research treatment.

Language: Английский

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Decoding the basis of histological variation in human cancer

Nature reviews. Cancer, Journal Year: 2023, Volume and Issue: 24(2), P. 141 - 158

Published: Dec. 22, 2023

Language: Английский

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