Introduction:Traditional Chinese Medicine (TCM) Combined with Methimazole (MMI) versus MMI Alone for Thyroid Function and Autoantibodies in Graves' Disease(GD). Methods:A systematic literature search was performed in PubMed, Cochrane Library, Web of Science, EMBASE, CNKI, VIP, CBM, and Wanfang databases up to June 2025 for RCTs comparing TCM plus MMI versus MMI alone. Study risk of bias was evaluated using the Cochrane tool. We assessed transitivity to ensure intervention comparability, verified consistency via node-splitting analysis, and planned sensitivity analysis according to risk-of-bias classification. A network meta-analysis was conducted in Stata 15.1 using a random-effects model. Results are reported as mean differences (MD) or standardized mean differences (SMD) with 95% confidence intervals (CI), and treatment efficacy was ranked using SUCRA values. Results:A network meta-analysis of 15 RCTs involving 1,317 GD patients and 14 TCM plus MMI regimens showed potential advantages over MMI alone in improving thyroid function indices and reducing selected autoantibodies, particularly TRAb and TPOAb. Adverse events were summarized descriptively because AE reporting was incomplete and heterogeneous across the included RCTs. Regarding SUCRA rankings, the Modified Huagan Decoction (MHD) + MMI ranked first for reducing FT3 (SUCRA = 93.4%), the Modified Xiaoyao Powder (MXYP) + MMI ranked first for reducing FT4 (SUCRA = 97.3%), and the Xiaoyao Powder (XYP) + MMI ranked first for regulating TSH (SUCRA = 96.3%). For decreasing TRAb, the MHD + MMI regimen ranked first (SUCRA = 88.2%), while for lowering TPOAb, the Huotan Jiangni Formula (HJF) + MMI showed the highest SUCRA ranking (SUCRA = 100%). Conclusion:TCM combined with MMI may have beneficial effects on thyroid function and selected autoantibody levels, particularly TRAb and TPOAb, in GD patients versus MMI alone. Among the evaluated regimens, MHD + MMI, MXYP + MMI, XYP + MMI, and HJF + MMI showed high SUCRA rankings for specific outcomes, including FT3, FT4, TSH, TRAb, and TPOAb. These findings suggest that TCM plus MMI may be a promising short-term adjunctive strategy for initial GD treatment, although safety evidence remains limited by incomplete and inconsistent AE reporting. Systematic review registration:https://www.crd.york.ac.uk/prospero/, identifier CRD420251151307.

Prostate cancer remains a leading cause of cancer-related mortality in men worldwide, with tumor heterogeneity, therapy resistance, and lineage plasticity posing significant clinical challenges. Androgen deprivation therapy (ADT), while initially effective, often culminates in castration-resistant prostate cancer, may fueled by castration-resistant prostate cancer stem cells (CSCs) with adaptive self-renewal and regenerative capacities. Emerging evidence implicates prostate CSCs as pivotal contributors to tumor heterogeneity, drug resistance, and disease recurrence. These stem subpopulations exhibit intrinsic adaptability through genetic, epigenetic, and microenvironmental reprogramming, enabling survival under androgen-deprived conditions and fostering clonal diversification. This review synthesizes current knowledge on the identity, regulation, and functional dynamics of prostate stem cells, emphasizing their role in shaping the tumor ecosystem. By dissecting the genetic drivers, epigenetic alteration and crosstalk with microenvironment, this review underscores critical triggers on prostate CSCs determination and differentiation. Additionally, we discuss emerging strategies to target prostate CSC-specific vulnerabilities, including molecular drivers of stemness and plasticity, to improve therapeutic outcomes for advanced prostate malignancies. This synthesis underscores the critical need to unravel prostate stem cells biology for developing precision therapies against prostate CSC-driven adaptation in prostate diseases.

Resistance to the BRAF inhibitor vemurafenib (PLX4032) limits its efficacy in thyroid cancer. Ubiquitin-specific peptidase 7 (USP7), a key regulator of oncogenic signaling, and USP7 inhibitor may help overcome drug resistance. This study investigated the combined efficacy of PLX4032 and the USP7 inhibitor P5091 in BRAFV600E-mutant thyroid cancer. Bioinformatics showed that USP7 and integrin subunit beta 3 (ITGB3), a MAPK/PI3K pathway gene, may jointly mediate resistance. In thyroid cancer cell lines, the combination treatment significantly reduced viability, proliferation, colony formation, migration, and invasion versus monotherapy. Moreover, the combination treatment can reduce viability and induce cell death in thyroid cancer organoids. Given USP7's role in oxidative stress and ferroptosis, we examined its involvement and found that P5091 induced ferroptosis via reactive oxygen species (ROS) elevation, glutathione peroxidase 4 (GPX4) downregulation, and elevated lipid peroxidation. These findings demonstrate that USP7 inhibition by P5091 enhances PLX4032 efficacy by promoting tumor suppression and ferroptosis in BRAFV600E-mutant thyroid cancer, offering a promising strategy to overcome resistance.

Background: Breast angiosarcoma (BA) is an extremely rare and highly aggressive breast malignancy, accounting for less than 1% of all breast malignancies and less than 5% of all soft tissue sarcomas. BA is associated with a poor prognosis due to a high risk of postoperative recurrence and future metastases, highlighting the importance of postoperative adjuvant therapy. However, the effectiveness of adjuvant chemotherapy for BA is still unclear, with relevant studies mainly based on case reports and small-scale studies. It is urgent to establish a reliable in vitro preclinical model to explore individualized treatment for BA. Methods: We reported a case of primary BA in a 36-year-old premenopausal woman who underwent a right-sided mastectomy. In order to investigate the most suitable drugs for this patient, we used the postoperative tumor specimen for digestion and preparation of organoid models. And the BA specimens and organoids were fixed and embedded to make paraffin sections. Both of them were then characterized by H&E and immunofluorescence staining. Subsequently, organoid models were used for screening of sensitive chemotherapy and targeted drugs. Results: The main clinical presentation of this case is a rapidly growing mass in the upper outer quadrant of the right breast, accompanied by slight purplish skin discoloration. The pathological diagnosis showed primary breast angiosarcoma, with immunohistochemical staining positive for CD34, CD31, ERG, and FLI-1, and a high Ki-67 index (60%). We successfully established an organoid model for BA, which could be passaged continuously and cryopreserved. The BA organoids closely recapitulated the histological features and captured the marker expression in the original tumor, including CD31, CD34, c-Myc, CD117, Ki-67, even after a long-term culture. The dose titration tests of 14 chemotherapeutic and targeted drugs displayed differential drug responses with diverse IC50 values. Among all the drugs, anthracycline, paclitaxel, and tyrosine kinase inhibitors such pazopanib showed excellent anti-tumor effects. Inversely, ifosfamide and endocrine drugs showed no obvious anti-tumor effects. Conclusion: This study indicate that patient-derived BA organoids may be a novel preclinical model to investigate personalized therapy for patients with BA. Citation Format: Xiaoling Liu, Meiyang Huang, Jicheng Li, Aishi Deng, Dong Chen. An organoid model derived from a patient with breast angiosarcoma [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P3-04-22.

The murine double minute 2 (MDM2)-p53 interaction inhibitor APG-115 demonstrates therapeutic potential in advanced malignancies. However, its molecular mechanism, especially for programmed death ligand 1 (PD-L1) immunotherapy modulation, remains poorly understood in thyroid cancer (TC). Herein, we conducted a series of in vitro and in vivo studies to investigate the therapeutic effect of APG-115 and the underlying molecular mechanisms in TC. We performed Cell Counting Kit (CCK-8) and cell scratch assay to assess the effect of APG-115 on the biological behavior of TC cells. Meanwhile, we performed animal experiments to investigate the therapeutic effect of APG-115 on TC in vivo. TC patient-derived organoids were further used to evaluate the potential value for clinical application of APG-115. Our results showed that APG-115 exhibited beneficial therapeutic effects in TC both in vitro and in vivo. Mechanistically, APG-115 restored the p53 antitumor effects by blocking MDM2-p53 binding and upregulating the PD-L1 expression. APG-115 downregulated Solute Carrier Family 7 Member 11 (SLC7A11) expression, contributing to lipid peroxidation and affecting PD-L1 expression in TC. Our study expands the clinical application value of APG-115 in cancer treatment, especially by further exploring the complex interplay between APG-115, PD-L1 immunotherapy, and ferroptosis.

Parathyroid carcinoma (PC) is a rare and aggressive malignancy, characterized by severe hypercalcemia and elevated parathyroid hormone (PTH) levels, making it particularly challenging to diagnose. In this case report, the patient’s PC was not diagnosed during the initial surgery. The diagnosis was delayed until two years later, when metastatic lesions appeared in the lungs, leading to repeat surgery and a retrospective review of the patient’s medical history. This case emphasizes the diagnostic difficulty of PC, particularly during the initial evaluation. Close postoperative follow-up is crucial for suspected cases. Upon biochemical evidence of recurrence, comprehensive systemic screening should be conducted, not only focusing on the neck but also on common metastatic sites such as the lungs, bones, and liver.

Endocrine cancers are a heterogeneous group of malignancies that originate from cells capable of secreting hormones. Examples include but are not limited to thyroid cancer, adrenocortical carcinoma, prostate cancer, and pancreatic cancer. Our limited understanding of endocrine cancers is partially due to constraints related to model systems, which cannot accurately replicate the pathogenesis of these tumors. Patient-derived organoids (PDOs) are clusters of multiple cell types that grow in a three-dimensional environment. They have become innovative models that faithfully reproduce genotype and phenotype of the tissues from which they originated, facilitating the prediction of patient treatment responses and guiding the development of precision medicine. This article provides a comprehensive review of the establishment of endocrine cancer PDOs and their applications in cancer research, drug screening, and personalized therapy. These excellent preclinical models have the potential to advance our understanding of endocrine cancers in basic research and clinical practice. In addition, we discuss the challenges related to current organoid technologies and provide future perspectives on the applications of organoids in precision medicine to improve the management of endocrine cancers.

Breast cancer (BC) is the most prevalent cancer among women around the world. Finding new and efficient drugs has become a crucial aspect of BC treatment. Liensinine diperchlorate (LIN) and artemisitene (ATT) are natural compounds with potential anti-cancer activities extracted from lotus (Nelumbo nucifera Gaertn) seeds and Artemisia annua, respectively. However, the synergistic anti-breast cancer effectiveness and mechanism of LIN and ATT remain unknown. This study intended to reveal the biological functions and underlying mechanism of combined LIN and ATT treatment in BC. Herein, we first reported that LIN and ATT synergistically mitigated the proliferation, migration as well as invasion of BC cells. Besides, LIN boosted the stimulatory effect of ATT on reactive oxygen species (ROS)-mediated apoptosis in BC cells. Interestingly, LIN and ATT synergistically attenuated the growth of BC patient-derived organoids. Moreover, LIN augmented the inhibitory efficacy of ATT on BC growth in vivo without obvious side effects. Furthermore, the inactivation of PI3K-AKT pathway and its regulated proteins contributed to the therapeutic role of LIN and ATT treatment in BC. Intriguingly, a prediction model constructed as per RNA sequencing data indicated that the combination of LIN and ATT treatment might ameliorate the prognosis of BC patients. In conclusion, our present investigation demonstrated that LIN and ATT synergistically inhibited BC cell proliferation, migration as well as invasion and enhanced ROS-mediated apoptosis via suppressing the PI3K-AKT signaling, and suggested that combining LIN and ATT treatment might be a promising choice for BC therapy.

Purpose This study aimed to explore novel targets for hepatocellular carcinoma (HCC) treatment by investigating the role of fatty acid metabolism. Methods RNA-seq and clinical data of HCC were obtained from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Bioinformatic analyses were employed to identify differentially expressed genes (DEGs) related to prognosis. A signature was then constructed using the Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression to classify HCC patients from the TCGA database into low-risk and high-risk groups. The predictive performance of the signature was evaluated through principal components analysis (PCA), Kaplan Meier (KM) survival analysis, receiver operating characteristics (ROC) curves, nomogram, genetic mutations, drug sensitivity analysis, immunological correlation analysis, and enrichment analysis. Single-cell maps were constructed to illustrate the distribution of core genes. Immunohistochemistry (IHC), quantitative real-time PCR (qRT-PCR), and western blot were employed to verify the expression of core genes. The function of one core gene was validated through a series of in vitro assays, including cell viability, colony formation, wound healing, trans-well migration, and invasion assays. The results were analyzed in the context of relevant signaling pathways. Results Bioinformatic analyses identified 15 FAMGs that were related to prognosis. A 4-gene signature was constructed, and patients were divided into high- and low-risk groups according to the signature. The high-risk group exhibited a poorer prognosis compared to the low-risk group in both the training (P < 0.001) and validation (P = 0.020) sets. Furthermore, the risk score was identified as an independent predictor of OS (P < 0.001, HR = 8.005). The incorporation of the risk score and clinicopathologic features into a nomogram enabled the effective prediction of patient prognosis. The model was able to effectively predict the immune microenvironment, drug sensitivity to chemotherapy, and gene mutation for each group. Single-cell maps demonstrated that FAMGs in the model were distributed in tumor cells. Enrichment analyses revealed that the cell cycle, fatty acid β oxidation and PPAR signaling pathways were the most significant pathways. Among the four key prognostically related FAMGs, Spermine Synthase (SMS) was selected and validated as a potential oncogene affecting cell cycle, PPAR-γ signaling pathway and fatty acid β oxidation in HCC. Conclusions The risk characteristics based on FAMGs could serve as independent prognostic indicators for predicting HCC prognosis and could also serve as evaluation criteria for gene mutations, immunity, and chemotherapy drug therapy in HCC patients. Meanwhile, targeted fatty acid metabolism could be used to treat HCC through related signaling pathways.

The mechanism underlying the development of renal cell carcinoma (RCC) remains unclear, and effective prevention and therapeutic measures are lacking. BIRC6, a protein inhibitor of apoptosis, has attracted great interest. Our data indicated that overexpression of BIRC6 elevated cell growth, colony formation, migration, and invasion of cultured RCC cells, while siRNA knockdown of BIRC6 suppressed these processes. Additionally, BIRC6 was highly expressed in RCC clinical samples along with a downregulated level of Axin. Immunoprecipitation assays found that BIRC6 interacted with Axin and the two proteins colocalized within the cytoplasm of RCC cells. Overexpression of BIRC6 promoted the ubiquitination modification of Axin, while genetic knockdown of BIRC6 suppressed it. Furthermore, overexpression of BIRC6 significantly promoted the turnover of Axin, suggesting BIRC6's inhibitory effect on Axin protein stability. BIRC6 was also upregulated in cancer stem-like cells of RCC and increased the drug resistance of RCC cells against sunitinib. Western blotting assays showed that the overexpression of BIRC6 upregulated CXCR4 protein expression and activated the β-catenin pathway. Two cell lines were then constructed with BIRC6 overexpressed by lentiviruses. Pharmacological administration of a Wnt/β-catenin inhibitor, XAV-939, or genetic knockdown of β-catenin inhibited cell growth, tumor sphere formation, colony formation, migration, and invasion of BIRC6-overexpressed cells. In vivo administration of XAV-939 markedly suppressed the tumorigenesis of BIRC6-overexpressed RCC cells in nude mice. In conclusion, we propose that BIRC6 activates the β-catenin signaling pathway via mediating the ubiquitination and degradation of Axin, promoting the growth, stemness, and drug resistance of RCC cells. This project aims to elucidate the role of BIRC6 as a potential therapeutic target and provide new insights into the clinical treatment of RCC.

Artemisitene (ATT) is a natural bioactive compound with anti-breast cancer activity. However, the direct target and clinical efficacy of ATT on breast cancer are still unclear. The current study aimed to identify the target protein and underlying mechanism of ATT in anti-breast cancer. Moreover, patient-derived organoids (PDOs) were employed to assess the clinical efficacy of ATT on breast cancer. Herein, molecular docking, molecular dynamics simulation, cellular thermal shift assay (CETSA) combined with Western blot, surface plasmon resonance (SPR) were applied to confirm the interactional target of ATT in breast cancer cells. Bioinformatics analysis, Western blot, flow cytometry, plasmid construction and lentivirus infection, chromatin immunoprecipitation (ChIP) assay, and quantitative real-time PCR (RT-qPCR) were performed to reveal the potential mechanism of ATT in treating breast cancer. PDOs were established to evaluate the clinical therapeutic efficiency of ATT on breast cancer. We found that ATT interacted with Farnesyl-diphosphate farnesyltransferase 1 (FDFT1) in breast cancer cells. Knockdown of FDFT1 induced NEDD4 expression and apoptosis in breast cancer cells. Overexpression of FDFT1 could rescue ATT-induced apoptosis, while interfering with FDFT1 expression decreased the level of RelA (NF-κB p65 subunit) in the nucleus in breast cancer cells. Knockdown of FDFT1 induced NEDD4 expression by regulating TNFR1/NF-κB pathway. Overexpression of FDFT1 could reverse the activation of ATT-induced TNFR1/NF-κB/NEDD4 pathway in breast cancer cells. Interestingly, the ChIP assay and RT-qPCR revealed that p65 could regulate NEDD4 transcription. Furthermore, ATT exhibited a broad-spectrum inhibitory effect on the growth of breast cancer PDOs with different pathological subtypes, and showed an excellent safety profile in comparison with that of conventional chemotherapy drugs. In summary, this work demonstrated that ATT targets FDFT1 to induce apoptosis of breast cancer cells through regulating TNFR1/NF-κB/NEDD4 pathway and suppresses breast cancer PDOs growth, which supported ATT as an effective and potential drug candidate for breast cancer treatment.

Pre-trained deep Transformers have had tremendous success in a wide variety of disciplines. However, in computational biology, essentially all Transformers are built upon the biological sequences, which ignores vital stereochemical information and may result in crucial errors in downstream predictions. On the other hand, three-dimensional (3D) molecular structures are incompatible with the sequential architecture of Transformer and natural language processing (NLP) models in general. This work addresses this foundational challenge by a topological Transformer (TopoFormer). TopoFormer is built by integrating NLP and a multiscale topology techniques, the persistent topological hyperdigraph Laplacian (PTHL), which systematically converts intricate 3D protein-ligand complexes at various spatial scales into a NLP-admissible sequence of topological invariants and homotopic shapes. Element-specific PTHLs are further developed to embed crucial physical, chemical, and biological interactions into topological sequences. TopoFormer surges ahead of conventional algorithms and recent deep learning variants and gives rise to exemplary scoring accuracy and superior performance in ranking, docking, and screening tasks in a number of benchmark datasets. The proposed topological sequences can be extracted from all kinds of structural data in data science to facilitate various NLP models, heralding a new era in AI-driven discovery.

Metastasis is the leading cause of death in patients with breast cancer. Detecting high-risk breast cancer, including micrometastasis, at an early stage is vital for customizing the right and efficient therapies. In this study, we propose an enzyme-free isothermal cascade amplification-based DNA logic circuit in situ biomineralization nanosensor, HDNAzyme@ZIF-8, for simultaneous imaging of multidimensional biomarkers in live cells. Taking miR-21 and Ki-67 mRNA as the dual detection targets achieved sensitive logic operations and molecular recognition through the cascade hybridization chain reaction and DNAzyme. The HDNAzyme@ZIF-8 nanosensor has the ability to accurately differentiate breast cancer cells and their subtypes by comparing their relative fluorescence intensities. Of note, our nanosensor can also achieve visualization within breast cancer organoids, faithfully recapitulating the functional characteristics of parental tumor. Overall, the combination of these techniques offers a universal strategy for detecting cancers with high sensitivity and holds vast potential in clinical cancer diagnosis.

PurposePhyllodes tumor of the breast is a kind of rare neoplasm, which accounts for less than 1% of all breast tumors. Malignant phyllodes tumor (MPT) is the highest risk subtype of phyllodes tumor, and is characterized by the tendency of local recurrence and distant metastasis. The prediction of prognosis and the individual therapy for MPT is still challenging. It's urgent to develop a new reliable in vitro preclinical model in order to understand this disease better and to explore appropriate anticancer drugs for individual patients.MethodsTwo surgically resected MPT specimens were processed for organoid establishment. MPT organoids were subsequently subjected to H&E staining, immunohistochemical analysis and drug screening, respectively.ResultsWe successfully established two organoid lines from different patients with MPT. The MPT organoids can well retain the histological features and capture the marker expression in original tumor tissues, including p63, vimentin, Bcl-2, CD34, c-Kit, and Ki-67, even after a long-term culture. The dose titration tests of eight typical chemotherapeutic drugs (paclitaxel, docetaxel, vincristine, doxorubicin, cisplatin, gemcitabine, cyclophosphamide, ifosfamide) on the two MPT organoid lines showed patient-specific drug responses and varying IC50 values. Of all the drugs, doxorubicin and gemcitabine showed the best anti-tumor effect on the two organoid lines.ConclusionOrganoids derived from MPT may be a novel preclinical model for testing personalized therapies for patients with MPT.

Backgrounds Papillary thyroid cancer (PTC), which is often driven by acquired somatic mutations in BRAF genes, is the most common pathologic type of thyroid cancer. PTC has an excellent prognosis after treatment with conventional therapies such as surgical resection, thyroid hormone therapy and adjuvant radioactive iodine therapy. Unfortunately, about 20% of patients develop regional recurrence or distant metastasis, making targeted therapeutics an important treatment option. Current in vitro PTC models are limited in representing the cellular and mutational characteristics of parental tumors. A clinically relevant tool that predicts the efficacy of therapy for individuals is urgently needed. Methods Surgically removed PTC tissue samples were dissociated, plated into Matrigel, and cultured to generate organoids. PTC organoids were subsequently subjected to histological analysis, DNA sequencing, and drug sensitivity assays, respectively. Results We established 9 patient-derived PTC organoid models, 5 of which harbor BRAF V600E mutation. These organoids have been cultured stably for more than 3 months and closely recapitulated the histological architectures as well as mutational landscapes of the respective primary tumors. Drug sensitivity assays of PTC organoid cultures demonstrated the intra- and inter-patient specific drug responses. BRAF V600E inhibitors, vemurafenib and dabrafenib monotherapy was mildly effective in treating BRAF V600E -mutant PTC organoids. Nevertheless, BRAF inhibitors in combination with MEK inhibitors, RTK inhibitors, or chemotherapeutic agents demonstrated improved efficacy compared to BRAF inhibition alone. Conclusions These data indicate that patient-derived PTC organoids may be a powerful research tool to investigate tumor biology and drug responsiveness, thus being useful to validate or discover targeted drug combinations.

BACKGROUND:Breast cancer (BC) is known as the most common cancer in women. Discovering novel and effective drugs is a priority for the treatment of BC. Oxypalmatine (OPT) is a natural protoberberine-type alkaloid isolated from Phellodendron amurense Rupr. (Rutaceae) with potential anti-cancer activity.PURPOSE:This investigation aimed to elucidate the biological role and potential mechanisms of OPT in BC cells, and intended to assess the therapeutic potential of OPT in BC patient-derived organoid models.METHODS:CCK-8 and EdU assays, and flow cytometry were used to test the activity of OPT against BC cells. In addition, patient-derived organoid models were constructed to assess the therapeutic efficiency of OPT in BC. Besides, network pharmacological analysis and RNA sequencing analysis were performed to predict the underlying anti-BC mechanism of OPT. Moreover, Western blot analysis was applied to test the expression of genes modulated by OPT.RESULTS:OPT attenuated the proliferation and DNA replication, and induced apoptosis in multiple BC cells. Interestingly, OPT also exerted a cytotoxic effect on BC organoids characterized as luminal A, HER2-overexpressing, and triple-negative subtypes, indicating that OPT was a potential broad-spectrum anticancer drug. Network pharmacological analysis suggested that OPT might affect signals contributing to BC progression, including PI3K/AKT, MAPK, and VEGFA-VEGFR2 signaling pathways. Moreover, bioinformatics analysis of data from our RNA sequencing suggested that PI3K/AKT was a downstream pathway of OPT in BC. Finally, OPT was shown to inactivate PI3K/AKT signaling pathway in BC cells by Western blot analysis.CONCLUSIONS:Collectively, our study demonstrated that OPT suppressed proliferation and induced apoptosis through mitigating the PI3K/AKT signaling pathway in BC cells. Moreover, our work first adopted BC organoid models to confirm OPT as an effective and promising drug, laying a foundation for the potential use of OPT in BC treatment.

Papillary thyroid cancer (PTC) is a common malignancy of the endocrine system, and its morbidity and mortality are increasing year by year. Traditional two-dimensional culture of cell lines lacks tissue structure and is difficult to reflect the heterogeneity of tumors. The construction of mouse models is inefficient and time-consuming, which is difficult to be applied to individualized treatment on a large scale. Clinically relevant models that recapitulate the biology of their corresponding parental tumors are urgently needed. Based on clinical specimens of PTC, we have successfully established patient-derived organoids by exploring and optimizing the organoid culture system. These organoids have been cultured stably for more than 5 passages and successfully cryopreserved and retried. Histopathological and genome analysis revealed a high consistency of the histological architectures as well as mutational landscapes between the matched tumors and organoids. Here, we present a fully detailed method to derive PTC organoids from clinical specimens. Using this approach, we have developed PTC organoid lines from thyroid cancer samples with a success rate of 77.6% (38/49) until now.

Cancer is a major health threat and a leading cause of human death worldwide. Surgical resection is the primary treatment for most cancers; however, some patients develop locoregional recurrence. Here, we developed an in situ cancer therapeutic system aimed to locally treat cancer and prevent postoperative recurrence. A functional scaffold, based on alginate/gelatin and crosslinked with copper ions, was fabricated by 3D printing and showed an excellent photothermal effect under near-infrared (NIR) irradiation. The combination of copper ions and NIR effectively killed thyroid cancer cells and patient-derived organoids, indicating a synergetic and broad-spectrum antitumor effect on thyroid cancer through the chemo-photothermal therapy. This implantable stent is designed to provide effective treatment in the vicinity of the tumor site and can be degraded without secondary surgery. The copper-loaded hydrogel scaffold may be a potential candidate for local cancer treatment and pave the way for precise and effective cancer therapy.