Establishment of patient‐derived organoids for guiding personalized therapies in breast cancer patients

International Journal of Cancer, Год журнала: 2024, Номер 155(2), С. 324 - 338

Опубликована: Март 27, 2024

Abstract Breast cancer has become the most commonly diagnosed cancer. The intra‐ and interpatient heterogeneity induced a considerable variation in treatment efficacy. There is an urgent requirement for preclinical models to anticipate effectiveness of individualized drug responses. Patient‐derived organoids (PDOs) can accurately recapitulate architecture biological characteristics origin tumor, making them promising model that overtake many limitations cell lines PDXs. However, it still unclear whether PDOs‐based testing benefit breast patients, particularly those with tumor recurrence or resistance. Fresh samples were surgically resected organoid culture. Primary PDOs subsequently subjected H&E staining, immunohistochemical (IHC) analysis, whole‐exome sequencing (WES) make comparisons. Drug sensitivity tests performed evaluate feasibility this predicting patient response clinical practice. We established 75 patient‐derived models. results IHC, WES revealed inherited histologic genetic their parental tissues. successfully predicted patient's response, cases exhibited consistency between PDOs' susceptibility test matched patient. conclude platform be potential tool used selection effective drugs guided personalized therapies patients advanced

Язык: Английский

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A synthetic lethal dependency on casein kinase 2 in response to replication-perturbing therapeutics in RB1-deficient cancer cells

Science Advances, Год журнала: 2024, Номер 10(21)

Опубликована: Май 23, 2024

Resistance to therapy commonly develops in patients with high-grade serous ovarian carcinoma (HGSC) and triple-negative breast cancer (TNBC), urging the search for improved therapeutic combinations their predictive biomarkers. Starting from a CRISPR knockout screen, we identified that loss of RB1 TNBC or HGSC cells generates synthetic lethal dependency on casein kinase 2 (CK2) surviving treatment replication-perturbing therapeutics such as carboplatin, gemcitabine, PARP inhibitors. CK2 inhibition RB1-deficient resulted degradation another RB family cell cycle regulator, p130, which led S phase accumulation, micronuclei formation, accelerated inhibition-induced aneuploidy mitotic death. was also effective primary patient-derived cells. It selectively prevented regrowth patient organoids after carboplatin niraparib. As about 25% HGSCs 40% TNBCs have lost expression, is promising approach overcome resistance standard large strata patients.

Язык: Английский

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A systematic review on the culture methods and applications of 3D tumoroids for cancer research and personalized medicine

Cellular Oncology, Год журнала: 2024, Номер unknown

Опубликована: Май 28, 2024

Cancer is a highly heterogeneous disease, and thus treatment responses vary greatly between patients. To improve therapy efficacy outcome for cancer patients, more representative patient-specific preclinical models are needed. Organoids tumoroids 3D cell culture that typically retain the genetic epigenetic characteristics, as well morphology, of their tissue origin. Thus, they can be used to understand underlying mechanisms initiation, progression, metastasis in physiological setting. Additionally, co-culture methods cancer-associated cells help interplay tumor its microenvironment. In recent years, have already helped refine treatments identify new targets therapy. Advanced culturing systems such chip-based fluidic devices bioprinting combination with been high-throughput applications personalized medicine. Even though organoid tumoroid complex vitro systems, validation results vivo still common practice. Here, we describe how both animal- human-derived novel vulnerabilities currently precision

Язык: Английский

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Single-Cell RNA Sequencing in Ovarian Cancer: Current Progress and Future Prospects

Progress in Biophysics and Molecular Biology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

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Organoid development and applications in gynecological cancers: the new stage of tumor treatment

Journal of Nanobiotechnology, Год журнала: 2025, Номер 23(1)

Опубликована: Янв. 16, 2025

Gynecologic cancers (GCs), including cervical cancer (CC), ovarian (OC), endometrial (EC), as well vulvar and vaginal cancers, represent major health threats to women, with increasing incidence rates observed globally. Conventional treatments, such surgery, radiation therapy, chemotherapy, are often hindered by challenges drug resistance recurrence, contributing high mortality rates. Organoid technology has emerged a transformative tool in research, offering vitro models that closely replicate the tumor cell architecture heterogeneity of primary cancers. Tumor-derived organoids preserve histological molecular characteristics original tumors, making them invaluable for studying biology, pathways, immune microenvironment. Furthermore, play crucial role biomarker discovery, screening, development personalized therapeutic strategies. In contrast traditional lines patient-derived xenograft (PDX) models, gynecologic accurately mirror genetic mutations specific gene expression profiles tumors. This review provides an overview recent advancements organoid highlighting their contributions understanding disease mechanisms, facilitating advancing precision medicine. It also addresses potential technology, focus on its treatment approaches GCs.

Язык: Английский

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piR-26441 inhibits mitochondrial oxidative phosphorylation and tumorigenesis in ovarian cancer through m6A modification by interacting with YTHDC1

Cell Death and Disease, Год журнала: 2025, Номер 16(1)

Опубликована: Янв. 18, 2025

Abstract Ovarian cancer (OC) is a heterogeneous cancer. In contrast to other tumor cells, which rely primarily on aerobic glycolysis (Warburg effect) as their energy source, oxidative phosphorylation (OXPHOS) also one of its major metabolic modes. Piwi-interacting RNAs (piRNAs) play regulatory function in various biological processes cells. However, the role and mechanisms piRNAs OC mitochondrial OXPHOS remain be elucidated. Here, we found that piR-26441 was aberrantly downregulated OC, overexpression suppressed malignant features cells growth xenograft model. Moreover, significantly reduced levels Furthermore, directly binds upregulates expression YTHDC1 increased m6A levels, thereby interacting with destabilize mRNA TSFM. The resultant TSFM loss complex I activity OXPHOS, leading dysfunction reactive oxygen species thus, DNA damage apoptosis inhibiting progression. Additionally, ago-piR-26441 metabolism patient-derived organoid Altogether, could inhibit cell via YTHDC1/TSFM signaling axis, underscoring significant importance context well offering potential therapeutic target.

Язык: Английский

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Tumor organoids in cancer medicine: from model systems to natural compound screening

Pharmaceutical Biology, Год журнала: 2025, Номер 63(1), С. 89 - 109

Опубликована: Фев. 1, 2025

The advent of tissue engineering and biomedical techniques has significantly advanced the development three-dimensional (3D) cell culture systems, particularly tumor organoids. These self-assembled 3D clusters closely replicate histopathological, genetic, phenotypic characteristics primary tissues, making them invaluable tools in cancer research drug screening. This review addresses challenges developing vitro models that accurately reflect heterogeneity explores application organoids research, with a specific focus on screening natural products for antitumor therapies. synthesizes information from major databases, including Chemical Abstracts, Medicinal Aromatic Plants ScienceDirect, Google Scholar, Scopus, PubMed Springer Link. Publications were selected without date restrictions, using terms such as 'organoid', 'natural product', 'pharmacological', 'extract', 'nanomaterial' 'traditional uses'. Articles related to agriculture, ecology, synthetic work or published languages other than English excluded. identifies key efficiency variability organoid generation discusses ongoing efforts enhance their predictive capabilities personalized medicine. Recent studies utilizing patient-derived compound are highlighted, demonstrating potential these new classes anticancer agents. integration presents promising approach discovering novel compounds elucidating mechanisms action.

Язык: Английский

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The atypical KRAS^Q22K mutation directs TGF‐β response towards partial epithelial‐to‐mesenchymal transition in patient‐derived colorectal cancer tumoroids

Molecular Oncology, Год журнала: 2025, Номер unknown

Опубликована: Март 11, 2025

Transforming growth factor beta (TGF‐β) exhibits complex and context‐dependent cellular responses. While it mostly induces tumor‐suppressive effects in early stages of tumorigenesis, tumor‐promoting properties are evident advanced disease. This TGF‐β duality is still not fully understood, whether supports invasion metastasis by influencing cancer cells directly, or rather through the stromal tumor compartment, remains a matter debate. Here, we utilized library colorectal (CRC) patient‐derived tumoroids (PDTs), representing spectrum stages, to study cell‐specific responses TGF‐β. Using conditions allowing for differentiation PDTs, observed TGF‐β‐induced early‐stage tumoroids, whereas more were less sensitive treatment. Notably, one tumoroid line harboring an atypical KRAS Q22K mutation underwent partial epithelial‐to‐mesenchymal transition (EMT), which was associated with morphological changes increased invasiveness. On molecular level, this accompanied elevated expression mesenchymal genes, as well deregulation pathways matrix remodeling cell adhesion. Our results suggest that cell‐intrinsic critical determining its effects.

Язык: Английский

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Mitochondrial fatty acid oxidation as the target for blocking therapy-resistance and inhibiting tumor recurrence: The proof-of-principle model demonstrated for ovarian cancer cells

Journal of Advanced Research, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

Cancer patients treated with current chemotherapeutic and targeted therapies frequently achieve partial remission, which ultimately relapse more aggressive, drug-resistant tumor phenotypes. To a certain extent, drug-tolerant persister (DTP) cells are responsible for residual tumors after systemic anticancer therapy the onset of acquired drug resistance. Therefore, novel targeting DTP to prevent resistance recurrence urgently needed. We aimed investigate traits key vulnerabilities ovarian cancer seek out potential therapeutic strategies. constructed paclitaxel-tolerant by exposing parental lethal dose paclitaxel. Proteomics analysis, in vitro vivo assays were performed identify biological processes that could serve as cells. Paclitaxel-tolerant found undergo metabolic reprogramming through upregulation fatty acid oxidation (FAO). Treatment FAO inhibitor ST1326 suppressed increased sensitivity paclitaxel Moreover, combination prevented satisfactory biosafety mouse model relapse, indicating disruption can improve efficacy paclitaxel-based cancer. Mechanistically, we treatment upregulated CEBPB, transcription factor induced expression FAO-related enzyme HADHA contributed elevation This study revealed an provided prospective paclitaxel-ST1326 may development superior long-term control future. Our research established conceptual framework advancing personalized approaches enhancing patient outcomes therapy.

Язык: Английский

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Zengmian Yiliu formula suppresses cell cycle in immune-rich ovarian cancer patient-derived organoids

Phytomedicine, Год журнала: 2025, Номер 141, С. 156721 - 156721

Опубликована: Апрель 5, 2025

Язык: Английский

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