Tumor organoids are tridimensional cell culture systems that are generated in vitro from surgically resected patients' tumors. They can be propagated in culture maintaining several features of the tumor of origin, including cellular and genetic heterogeneity, thus representing a promising tool for precision cancer medicine. Here, we established patient-derived tumor organoids (PDOs) from different breast cancer subtypes (luminal A, luminal B, human epidermal growth factor receptor 2 (HER2)-enriched, and triple negative). The established model systems showed histological and genomic concordance with parental tumors. However, in PDOs, the ratio of diverse cell populations was frequently different from that originally observed in parental tumors. We showed that tumor organoids represent a valuable system to test the efficacy of standard therapeutic treatments and to identify drug resistant populations within tumors. We also report that inhibitors of mechanosignaling and of Yes-associated protein 1 (YAP) activation can restore chemosensitivity in drug resistant tumor organoids.
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http://dx.doi.org/10.3390/cancers12123869 | DOI Listing |
Nat Cell Biol
January 2025
Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA.
Glioblastoma (GBM) is defined by heterogeneous and resilient cell populations that closely reflect neurodevelopmental cell types. Although it is clear that GBM echoes early and immature cell states, identifying the specific developmental programmes disrupted in these tumours has been hindered by a lack of high-resolution trajectories of glial and neuronal lineages. Here we delineate the course of human astrocyte maturation to uncover discrete developmental stages and attributes mirrored by GBM.
View Article and Find Full Text PDFInt J Biol Macromol
January 2025
Department of Gastroenterology, Changhai Hospital, Naval Medical University, No. 168 Changhai Road, Shanghai 200433, PR China. Electronic address:
In this paper, a pH-sensitive chitosan-grafted phenylboronic acid (CS-BA)/polyvinyl alcohol (PVA) hydrogel was constructed based on dynamic borate bonding for loading chemotherapeutic drug cisplatin (CDDP) and divalent Cu (CS-BA/PVA-Cu-CDDP). The hydrogel can respond and degrade specifically in the simulative acidic tumor microenvironment (TME), and the released Cu can deplete glutathione (GSH) in tumor cells and generate Cu. It is worth noting that, Cu can further catalyze the Fenton-like reaction to generate cancer cell-toxic hydroxyl radicals (OH•).
View Article and Find Full Text PDFSTAR Protoc
January 2025
Division of Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-0071, Japan; Department of Regenerative Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan; Department of Gastrointestinal Surgery, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama, Kanagawa 241-8515, Japan.
Pancreatic ductal adenocarcinoma (PDAC) organoids that simulate the tumor microenvironment (TME) are an effective tool to identify how TME affects PDAC malignancy. We present a protocol for generating a fused pancreatic cancer organoid (FPCO) that partly reproduces the TME, including heterogeneous cancer-associated fibroblasts (CAFs), using patient-derived PDAC cells and human-induced pluripotent cell-derived endothelial and mesenchymal cells. We also describe the procedure for analyzing FPCO characteristics.
View Article and Find Full Text PDFCells
December 2024
School of Medicine and Life Sciences, Far Eastern Federal University, 690922 Vladivostok, Russia.
Gliomas are a group of primary brain tumors characterized by their aggressive nature and resistance to treatment. Infiltration of surrounding normal tissues limits surgical approaches, wide inter- and intratumor heterogeneity hinders the development of universal therapeutics, and the presence of the blood-brain barrier reduces the efficiency of their delivery. As a result, patients diagnosed with gliomas often face a poor prognosis and low survival rates.
View Article and Find Full Text PDFBiomedicines
November 2024
Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, China.
When a patient has two or more primary tumors, excluding the possibility of diffuse, recurrent, or metastatic, they can be defined as having multiple primary malignant neoplasms (MPMNs). Moreover, cases of three primary urinary tract tumors are very rare. Here, we reported a patient of MPMNs with four primary tumors, including three urinary tract cancers (renal cancer, prostate cancer, and bladder cancer) and lung cancer.
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