Xu H, Huang W, Luo H
… +5 more, Zhang A, Guo Y, Peng G, Wu T, He Y
Clin Med Insights Oncol
· 2026 · PMID 42368680
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BACKGROUND: Augmented reality navigation (ARN) has been increasingly applied in laparoscopic liver surgery to improve anatomical orientation and surgical precision. However, its clinical value compared with conventional...BACKGROUND: Augmented reality navigation (ARN) has been increasingly applied in laparoscopic liver surgery to improve anatomical orientation and surgical precision. However, its clinical value compared with conventional anatomical liver resection (ALR) and non-anatomical liver resection (NALR) remains unclear. METHOD: This retrospective single-center study included 96 patients with hepatocellular carcinoma who underwent laparoscopic hepatectomy from January 2019 to December 2021. Patients were divided into three groups: ARN-assisted laparoscopic nonanatomic hepatectomy (Group A, n=28), laparoscopic anatomical hepatectomy without navigation (Group B, n=35), and laparoscopic nonanatomic hepatectomy without navigation (Group C, n=33). Baseline demographic, clinical, tumor, and segmental distributions were comparable among groups. Postoperative outcomes, postoperative complications, and 36-month follow-up data were analyzed. RESULT: Preoperative characteristics did not significantly differ among the three groups. Operative time was significantly shorter in Group A than in Group B (=0.003) and Group C (=0.039). Median intraoperative blood loss in Group A was 125ml, which was 175ml less than in Group B (=0.048) and 75 ml less than in Group C (=0.049). On postoperative day 7, median α-fetoprotein was lower (0.049) in group A (4.26 iu/ml) than in group C (5.82 iu/ml). 3-Year overall survival did not significantly differ among three groups. 3-Year tumor-free survival rates were 60.7% in group A, 62.9% in group B, and 36.3% in group C, with Group A and B showing significantly better tumor-free survival than group C ( 0.041; 0.024). Postoperative complication rates were similar across groups. CONCLUSION: In this cohort, ARN-assisted laparoscopic nonanatomic hepatectomy was associated with reduced operative time and blood loss and demonstrated short-term oncological outcomes similar to anatomical hepatectomy. These findings suggest that ARN may enhance the effectiveness of non-anatomical hepatectomy; however, confirmation in larger prospective studies is required.
Ikoma T, Araki K, Kitagawa M
… +17 more, Makihara N, Nagata Y, Fujii K, Okuno Y, Kamisako K, Okazaki Y, Nakanishi K, Sanada Y, Yoshida K, Nakahama K, Takeyasu Y, Katsushima U, Yamanaka Y, Ikeda S, Yoshioka H, Shimizu T, Kurata T
Mol Ther Oncol
· 2026 Sep · PMID 42368624
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Angiotensin II receptor type 1 () has emerged as a potential modulator of the tumor microenvironment, yet its role in the immunotherapy response in non-small cell lung cancer (NSCLC) remains unclear. We performed a compr...Angiotensin II receptor type 1 () has emerged as a potential modulator of the tumor microenvironment, yet its role in the immunotherapy response in non-small cell lung cancer (NSCLC) remains unclear. We performed a comprehensive analysis using bulk RNA sequencing and single-cell RNA sequencing (scRNA-seq) datasets. Functional validation included IHC for and phospho-SMAD2/3 co-localization. The clinical impact of angiotensin receptor blocker (ARB) use was assessed in patients receiving immune checkpoint blockade (ICB) alone or combined with chemo-immunotherapy. -high expression in NSCLC was associated with pronounced pathway modulation, including significant upregulation of TGF-β, etc. scRNA-seq analysis revealed that was predominantly localized in cancer-associated fibroblasts (CAFs). IHC validation in NSCLC specimens ( = 14) demonstrated a strong correlation between stromal AGTR1 and phospho-SMAD2/3 expression and ARB-treated patients showed significantly reduced stromal and pSMAD2/3 expression. Clinically, ARB treatment showed no benefit in ICB monotherapy but significantly improved PFS in chemo-immunotherapy (HR = 0.70, = 0.01), especially in non-squamous (non-Sq) histology with PD-L1≥1% (HR = 0.52, = 0.01). AGTR1 is predominantly expressed in CAFs and is suggestive of a correlation with TGF-β-related immunosuppressive features in NSCLC. The combination of ARB with chemo-immunotherapy may enhance therapeutic efficacy through targeting that axis in CAFs, specifically in non-Sq NSCLC patients.
Qiao K, Huang Y, Chua D
… +7 more, Qu J, Liao Q, Wang G, Tan NS, Liao S, Li L, Zhang G
Mol Ther Oncol
· 2026 Sep · PMID 42358378
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Lung adenocarcinoma (LUAD) is a leading cause of cancer-related mortality, driven by extensive tumor heterogeneity and therapy resistance. Conventional models fail to capture the dynamic interactions between cancer cells...Lung adenocarcinoma (LUAD) is a leading cause of cancer-related mortality, driven by extensive tumor heterogeneity and therapy resistance. Conventional models fail to capture the dynamic interactions between cancer cells and the tumor microenvironment (TME), limiting therapeutic advancements. Here, we present a tricomponent organoid platform integrating patient-derived lung cancer tumoroids (LCTs), normal lung organoids (LOs), and field-cancerized fibroblasts to dissect LUAD heterogeneity and treatment resistance mechanisms. This platform uniquely enables the simultaneous investigation of tumor-specific vulnerabilities, stromal contributions to drug resistance, and normal tissue toxicity. Spatial and bulk transcriptomic analyses reveal LUAD-specific gene signatures and highlight cancer-associated fibroblasts (CAFs) as key drivers of a pro-tumorigenic TME, reinforcing tumor survival and recurrence. Functional drug screening demonstrates that LCTs exhibit selective sensitivity to pemetrexed while fibroblasts remain universally resistant, underscoring stromal barriers to therapy. The inclusion of LOs allows direct assessment of drug toxicity on healthy lung tissue, bridging a critical gap in preclinical modeling. By capturing the tumor-stroma interplay with patient specificity, this organoid platform advances precision oncology, paving the way for more effective therapeutic strategies targeting both LUAD cells and the supportive microenvironment.
Choudhury PR, Chakravarti M, Bera S
… +20 more, Arora P, Sultana J, Khan MA, Biradar R, Guha A, Dhar S, Ghosh I, Ganguly N, Lasure A, Kashyap P, Das J, Mandal B, Das P, Sarkar A, Datta D, Nandi S, Alam N, Baral R, Banerjee S, Bose A
Mol Ther Oncol
· 2026 Sep · PMID 42358377
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Early inception of hypercholesterolemia has led to prevalent statin pre-exposure among cancer patients. Furthermore, emerging associations between increased circulating cholesterol, dyslipidemia, and cancer recurrence ha...Early inception of hypercholesterolemia has led to prevalent statin pre-exposure among cancer patients. Furthermore, emerging associations between increased circulating cholesterol, dyslipidemia, and cancer recurrence have spurred the repurposing of statins to combat cancer. However, the mechanistic impact of statin pre-exposure on cancer progression remains unclear. Here, our retrospective study with triple-negative breast cancer (TNBC) patients showed that atorvastatin pre-exposure promotes recurrence-free survival. Atorvastatin pre-exposure in TNBC patients and a preclinical high-fat diet-induced hypercholesterolemic murine tumor model lowered intratumoral 27-hydroxycholesterol (27HC) concentration, as estimated by LC-MS/MS. Within the tumor microenvironment, elevated 27HC interacted with estrogen receptor alpha (ERα) on dendritic cells (DCs), hindering DC maturation, migration, and antigen presentation. Atorvastatin reduced ERα expression on DCs and remediated 27HC-ERα-induced DC dysfunctions, improved DC-mediated T cell priming, thereby facilitating tumor restriction when adoptively transferred to 4T1-bearing NOD/SCID/IL2Rγ mice. Targeted intratumoral knockdown of (rate-determining enzyme for 27HC production) alongside atorvastatin pre-exposure uplifted cDC1 functionality. Atorvastatin pre-treatment exerts its action by reducing the availability of intratumoral 27HC and expression of ERα on DCs, which eventually enhances DC functionality and restores their efficiency to prime anti-tumor CD8 T cell responses. Therefore, atorvastatin pre-exposure adjunct to 27HC-ERα inhibition may serve as an effective immunotherapeutic intervention in TNBC.
Wang J, Fang Z, Wang J
… +7 more, Han X, Feng F, Zhang R, Han B, Sun G, Zhang Y, Ni S
Mol Ther Oncol
· 2026 Sep · PMID 42358376
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Pituitary corticotroph tumors are the primary cause of Cushing's disease. Even after transsphenoidal surgery, residual tumor cells frequently persist, leading to a recurrence rate of approximately 20%. However, safe and...Pituitary corticotroph tumors are the primary cause of Cushing's disease. Even after transsphenoidal surgery, residual tumor cells frequently persist, leading to a recurrence rate of approximately 20%. However, safe and effective adjuvant treatments for these residual lesions are lacking. In this study, we analyzed single-cell RNA sequencing data to characterize the transcriptional profile of corticotroph tumors. On the basis of the high activity of the promoter and its transcriptional regulators, we designed an adeno-associated virus vector carrying the pro-apoptotic gene , with expression controlled by the promoter for lineage-specific targeting. We also developed an injectable, self-assembling peptide hydrogel for the sustained local delivery of the gene and tested its therapeutic efficacy in subcutaneous and post-resection mouse models. Results showed the promoter drove selective expression in corticotroph tumor cells, inducing mitochondrial membrane potential loss and apoptosis . , the virus suppressed tumor growth and lessened systemic tumor effects; when delivered via the hydrogel into surgical cavities, it completely eliminated residual tumors without detectable toxicity in major organs. This targeted, localized strategy, thus has translational potential as an adjuvant therapy for reducing the recurrence of Cushing's disease.
Breast cancer remains one of the leading causes of cancer-related mortality among women worldwide. Although advances in early diagnosis and conventional therapies have significantly improved the prognosis in many cases,...Breast cancer remains one of the leading causes of cancer-related mortality among women worldwide. Although advances in early diagnosis and conventional therapies have significantly improved the prognosis in many cases, certain aggressive subtypes such as triple-negative breast cancer continue to pose major clinical challenges due to the absence of specific therapeutic targets. Therefore, we believe that exploring novel strategies for the development and application of immunotherapy may change the paradigm for this type of tumor. Immunotherapy aims to activate the patient's own immune system to recognize and eliminate tumor cells more effectively and selectively, improving immunological memory. Based on a structured review of scientific literature and therapeutic clinical trials published in the main scientific databases, including studies of different clinical phases and stages of the disease, from early-stage to metastatic breast cancer, we conclude that immune checkpoint inhibitors, especially when combined with chemotherapy and administered to patients with positive biomarkers, such as PD-L1 expression, provide significant clinical benefits. In addition, therapeutic vaccines continue to be studied as a promising approach to preventing relapses in high-risk patients when combined with other immunotherapy agents. This represents a major advance in the treatment of the most aggressive subtypes of breast cancer, positioning immunotherapy as one of the most promising treatments.
Anaplastic thyroid carcinoma (ATC) is a highly aggressive malignancy characterized by rapid progression, restricted therapeutic options, and dismal prognosis. Conventional therapeutic modalities demonstrate limited effic...Anaplastic thyroid carcinoma (ATC) is a highly aggressive malignancy characterized by rapid progression, restricted therapeutic options, and dismal prognosis. Conventional therapeutic modalities demonstrate limited efficacy, especially for unresectable or metastatic cases. Recent advancements in molecular profiling have revolutionized ATC management, facilitating the development of novel targeted therapies, immunotherapies, and multimodal regimens. Growing clinical evidence indicates these innovative approaches may enhance locoregional control, increase surgical candidacy in select patients, and extend overall survival. Incorporating molecular-guided therapies into multidisciplinary care is fundamentally transforming ATC management. Nevertheless, therapeutic resistance, intratumoral heterogeneity, and the paucity of large-scale prospective trials remain major obstacles. Future efforts should focus on optimizing combinatorial strategies and developing robust biomarker-driven algorithms to improve clinical outcomes in ATC.
BACKGROUND: Bispecific T-cell engagers (BiTEs) and chimeric antigen receptor (CAR) T-cell therapies have transformed the management of hematologic malignancies, including relapsed/refractory multiple myeloma (RRMM), lymp...BACKGROUND: Bispecific T-cell engagers (BiTEs) and chimeric antigen receptor (CAR) T-cell therapies have transformed the management of hematologic malignancies, including relapsed/refractory multiple myeloma (RRMM), lymphomas, and leukemias. These approaches enable targeted cytotoxicity through T-cell redirection and engineered cellular activity, achieving high response rates in heavily pretreated populations. Data presented at the 2025 Immune Cell Effector Therapies (ICE-T) Symposium highlighted expansion beyond B-cell maturation antigen (BCMA) to additional targets such as GPRC5D and FcRH5, alongside emerging multitarget and next-generation constructs aimed at improving durability and overcoming resistance. METHODS: This narrative review summarizes key findings from the 2025 ICE-T Symposium, integrating data from clinical trials, real-world studies, and contemporary guideline-based management, with a focus on efficacy, safety, sequencing, and emerging therapeutic platforms. RESULTS: Across hematologic malignancies, immune-based therapies demonstrated substantial and clinically meaningful activity, with outcomes varying by disease subtype, target antigen, and therapeutic platform. In multiple myeloma, BCMA-directed bispecific antibodies, including teclistamab and elranatamab, achieved overall response rates (ORRs) of approximately 63% and 61%, respectively, in heavily pretreated populations, with median progression-free survival (PFS) of approximately 11 to 17 months across pivotal studies. Talquetamab demonstrated ORR of approximately 73% to 74% in the MonumenTAL-1 study (NCT03399799), supporting efficacy in post-BCMA settings. Cevostamab has shown promising early-phase activity, with response rates of approximately 55% to 60% at higher dose levels, reflecting the expansion of therapeutic targets beyond BCMA. In B-cell lymphomas, CD19-directed CAR T-cell therapies, including axicabtagene ciloleucel and lisocabtagene maraleucel, produced high response rates with durable remissions in relapsed/refractory large B-cell lymphoma, with long-term follow-up demonstrating sustained survival in a subset of patients. Among bispecific antibodies, epcoritamab achieved an ORR of approximately 60% to 65%, whereas glofitamab demonstrated an ORR of approximately 45% to 50% in heavily pretreated populations, supporting their role as effective off-the-shelf therapeutic options. In acute lymphoblastic leukemia, CD19-directed CAR T-cell therapies, including tisagenlecleucel and brexucabtagene autoleucel, achieved high rates of remission with deep measurable residual disease negativity, supporting their role as definitive or bridging strategies in relapsed disease. Beyond hematologic malignancies, early-phase data highlighted the expansion of T cell-redirecting therapies into solid tumors. The DLL3-directed bispecific antibody tarlatamab demonstrated clinically meaningful activity in relapsed small cell lung cancer and has received accelerated regulatory approval based on response rate and durability. Safety profiles were broadly consistent across platforms. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were frequent but predominantly low grade and manageable with IL-6 blockade and corticosteroids. Infections and prolonged cytopenias represented the principal drivers of morbidity, emphasizing the need for structured supportive care. Contemporary recommendations from the NCCN and International Myeloma Working Group support proactive toxicity mitigation, antimicrobial prophylaxis, and multidisciplinary management. Emerging strategies, including trispecific antibodies, dual-target CAR T-cell constructs, and allogeneic "off-the-shelf" cellular therapies, demonstrated promising early efficacy and represent key approaches to improving durability, overcoming resistance, and expanding access across hematologic malignancies. CONCLUSIONS: T cell-redirecting therapies represent a central pillar in modern oncology, delivering high response rates across hematologic malignancies with expanding roles in earlier treatment settings. Future progress will depend on improving durability, optimizing sequencing, mitigating toxicity, and enhancing real-world deliverability through next-generation and multitarget platforms.
Okada H, Nio K, Ohno N
… +15 more, Masuo Y, Hirokawa T, Shimakami T, Miyati T, Takamura H, Ohta T, Kitao A, Kobayashi S, Gabata T, Matsui O, Kato Y, Seiki M, Honda M, Kaneko S, Yamashita T
Mol Ther Oncol
· 2026 Jun · PMID 42318058
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Activation of tumor suppressors represents an attractive strategy for cancer treatment. Hepatocyte nuclear factor 4 alpha (HNF4A) functions as a tumor suppressor in the liver by inhibiting hepatocyte proliferation; howev...Activation of tumor suppressors represents an attractive strategy for cancer treatment. Hepatocyte nuclear factor 4 alpha (HNF4A) functions as a tumor suppressor in the liver by inhibiting hepatocyte proliferation; however, no effective agonists have been identified. Here, we aimed to identify novel ligands for HNF4A and evaluate their role in hepatocarcinogenesis. We identified polyprenoic acid (PA, peretinoin) as the first ligand capable of directly binding HNF4A. Reanalysis of prior clinical trial data revealed that PA suppressed the progression of dysplastic nodules (DNs) to hepatocellular carcinoma (HCC), while showing no effect on local HCC recurrence after initial treatment. Consistently, PA inhibited DN growth but not established HCC in Pdgf-C transgenic mice. Mechanistically, PA selectively bound to the HNF4A P1 isoform, enhancing its transcriptional activity and upregulating hepatocyte maturation markers (ALB, TTR, and SLCO1B3), while suppressing alpha-fetoprotein expression driven by the HNF4A P2 isoform. Importantly, hepatocyte-specific knockdown or lipid-nanoparticle-mediated siRNA abrogated the protective effects of PA. These findings establish HNF4A as a pharmacologically controllable tumor suppressor and highlight PA-like compounds as promising agents for preventing liver carcinogenesis.
Taguchi S, Fukuhara H, Cai S
… +7 more, Li XK, Naito A, Kakutani S, Takeshima Y, Miyakawa J, Kume H, Todo T
Mol Ther Oncol
· 2026 Jun · PMID 42318057
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Oncolytic herpes simplex virus type 1 (HSV-1), including marketing-approved G47Δ, elicits antitumor immunity via facilitating antigen presentation during immune-mediated clearance of infected tumor cells. Dendritic cell...Oncolytic herpes simplex virus type 1 (HSV-1), including marketing-approved G47Δ, elicits antitumor immunity via facilitating antigen presentation during immune-mediated clearance of infected tumor cells. Dendritic cell (DC) therapy should therefore enhance oncolytic HSV-1 efficacy, but its clinical application is hindered by the need to generate autologous DCs. Induced pluripotent stem cell (iPSC) technologies offer a scalable and standardized source of DCs. Here, we investigate the therapeutic potential of combining iPSC-derived DCs (iPSDCs) with an interleukin-12-expressing oncolytic HSV-1, T-mfIL12. iPSDCs, generated from a murine embryonic fibroblast-derived iPSC line, possess characteristics and functions comparable to bone marrow-derived DCs (BMDCs), including costimulatory molecule expression, antigen uptake capacity, and the ability to stimulate CD8 and CD4 T cells isolated from ovalbumin-specific transgenic mice both and . In a syngeneic murine bladder cancer model, iPSDCs markedly enhanced the efficacy of intratumorally inoculated T-mfIL12, eliciting augmented immune responses including intratumoral T cell infiltration, tumor-responsive T cell activation, and maturation of DCs, similarly to BMDCs. The results indicate that iPSDCs can serve as an effective and practical alternative to conventional DCs in oncolytic virus immunotherapy. The combination of T-mfIL12 with iPSDCs offers a promising and clinically applicable cancer treatment strategy.
Xue W, Wang Y, Smirnova AV
… +4 more, Malakhov PA, Pustovalova M, Kuzmin DV, Leonov S
Mol Ther Oncol
· 2026 Jun · PMID 42318056
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The TGF-β signaling pathway has both tumor-suppressive and metastasis-promoting effects in cancer, yet the molecular determinants governing this switch remain unclear. Here, we investigated the miR-16-1-3p/MDM2/p53 axis...The TGF-β signaling pathway has both tumor-suppressive and metastasis-promoting effects in cancer, yet the molecular determinants governing this switch remain unclear. Here, we investigated the miR-16-1-3p/MDM2/p53 axis as a potential regulator of TGF-β/Smad signaling output in osteosarcoma. miR-16-1-3p overexpression alone markedly reduced the proliferative and clonogenic potential of U2OS cells, while its combination with TGF-β treatment strongly enhanced G1-phase arrest and nearly abolished tumor growth capacity. miR-16-1-3p inhibited TGF-β-induced actin remodeling and epithelial-mesenchymal transition (EMT)-associated changes. While TGF-β promoted both 2D and 3D migration, miR-16-1-3p overexpression, alone or combined with TGF-β, counteracted its pro-migratory effects. Mechanistically, miR-16-1-3p reduced MDM2 expression and stabilized p53, which was associated with enhanced p21 induction and suppression of proliferative responses under TGF-β stimulation. Co-administration of TGF-β and miR-16-1-3p markedly increased cisplatin sensitivity in wild-type U2OS cells and reduced tumor nodule volume, Ki67 expression, and metastasis in the chicken chorioallantoic membrane model. Collectively, these findings suggest that miR-16-1-3p biases TGF-β signaling output toward anti-growth responses, while attenuating pro-migratory effects through MDM2 inhibition and p53 stabilization, providing a mechanistic rationale for improving therapeutic responses in osteosarcoma.
Feng N, Zhou J, Xi Z
… +3 more, Huang T, Xu M, Zheng X
Clin Med Insights Oncol
· 2026 · PMID 42312220
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BACKGROUND: The incidence of papillary thyroid cancer (PTC) has risen sharply over the past several decades. Early identification of high-risk PTC is crucial to mitigate the societal burden associated with its overdiagno...BACKGROUND: The incidence of papillary thyroid cancer (PTC) has risen sharply over the past several decades. Early identification of high-risk PTC is crucial to mitigate the societal burden associated with its overdiagnosis. ER-phagy, a selective form of autophagy targeting the endoplasmic reticulum, is categorized into macro-ER-phagy and micro-ER-phagy. To date, the role of ER-phagy receptors and their impact on risk stratification and progression in thyroid cancer remain unclear. METHODS: This study employed an integrative approach combining bioinformatics analysis with wet-lab molecular biology experiments. Transcriptomic and clinical data from TCGA were processed using Xiantaoxueshu, GSCA, TIMER, and TISIDB platforms to assess differential expression, survival, ROC characteristics, and KEGG/GO enrichment, as well as immune infiltration. In vitro, shRNAs targeting RTN3, SEC62, or ATL3 were transfected into TPC-1 and CAL-62 cells to silence gene expression, validated by RT-qPCR and Western Blot. Cell proliferation, migration, and invasion were assessed by CCK-8, EdU, colony formation, wound healing, and Transwell assays. All experiments were performed in at least three independent replicates, and the resulting data were subjected to statistical analysis. Data were analyzed using SPSS 18.0 and GraphPad Prism 9.3.0. Quantitative results are presented as mean ± SEM. Independent-samples t-tests, univariate/multivariate Cox regression and LASSO Cox regression were used; P < 0.05 was considered significant. RESULTS: Comprehensive analysis of all ER-phagy receptors using public databases revealed that several receptors significantly impact the diagnosis and prognosis of thyroid cancer. We also characterized the mutation and methylation pattern of these receptors. Furthermore, these genes were also closely associated with immune infiltration in thyroid cancer. Of note, RTN3, SEC62 and ATL3 appeared to have distinct importance in thyroid cancer. All three genes were downregulated and their reduced expression was significantly related to poor survival in thyroid cancer. Receiver Operating Characteristic (ROC) curve analysis demonstrated that these markers hold substantial promise for thyroid cancer diagnosis, particularly RTN3 and SEC62. Immune-related analysis indicated a strong correlation with immune infiltration, implying a potential role in modulating the immune landscape of thyroid cancer. Functional assays demonstrated that knockdown of RTN3, SEC62, and ATL3 promoted proliferation and metastasis of thyroid cancer cells in vitro. Western blot analysis indicated that this process is likely mediated by the Epithelial-Mesenchymal Transition (EMT). CONCLUSION: In summary, our findings indicate that ER-phagy represents a promising avenue for thyroid cancer diagnosis. Specifically, RTN3, SEC62, and ATL3 were found to suppress the proliferation and metastasis of thyroid cancer cells, underscoring their pivotal roles in disease progression.