Screening of organoids derived from patients with breast cancer implicates the repressor NCOR2 in cytotoxic stress response and antitumor immunity

Tsai, Kelvin K.; Huang, Shu-Ching; Northey, Jason J.; Liao, Wen‐Ying; Hsu, Chung–Chi; Cheng, Li-Hsin; Werner, Michael; Chuu, Chih‐Pin; Chatterjee, Chandrima; Lakins, Jonathon N.; Weaver, Valerie M.

doi:10.1038/s43018-022-00375-0

Cited by 23 publications

(11 citation statements)

References 74 publications

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“…25 The fusion partner, nuclear receptor corepressor 2 (NCOR2), is a member of a family of thyroid hormone and retinoic acid receptor nuclear co-repressors that functions as a transcriptional silencer of target genes. 26 However, the implication of NCOR2 alterations alone has not been described in cases of sarcoma.…”

Section: Discussionmentioning

confidence: 99%

Keratin-Positive Giant Cell-Rich Tumor of Bone Harboring an HMGA2::NCOR2 Fusion: Two Cases, Including a Patient With Metastatic Disease, and Review of the Literature

et al. 2023

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Giant cell-rich lesions of bone represent a heterogeneous group of entities which classically include giant cell tumor of bone, aneurysmal bone cyst, nonossifying fibroma, and Brown tumor of hyperparathyroidism. A recently described subset of giant cell-rich tumors involving bone and soft tissue has been characterized by recurrent HMGA2::NCOR2 fusions and keratin expression. The overlapping clinical, radiographic, and morphological features of these giant cell-rich lesions provide a unique diagnostic challenge, particularly on biopsy. We present 2 additional cases of keratin-positive giant cell-rich tumor of bone with HMGA2::NCOR2 fusions, including 1 patient who developed metastatic disease.

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Section: Discussionmentioning

confidence: 99%

Keratin-Positive Giant Cell-Rich Tumor of Bone Harboring an HMGA2::NCOR2 Fusion: Two Cases, Including a Patient With Metastatic Disease, and Review of the Literature

et al. 2023

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“… 26 Moreover, the expression level of NCOR2 was associated with poor prognosis, chemoresistance, distant metastasis, and tumor recurrence of breast cancer. 27 , 28 ABCC5 as a member of ATP-binding cassette (ABC) transporter family is involved in efflux of several endogenous substances, toxins, and therapeutic agents, such as cisplatin methotrexate, and 5-Fu. On the other hand, ABCC5 has a role in chemoresistance of several cancers, such as hepatocellular carcinoma, breast cancer, and colorectal cancer.…”

Section: Discussionmentioning

confidence: 99%

Identification of Prognostic Biomarkers for Breast Cancer Metastasis Using Penalized Additive Hazards Regression Model

et al. 2023

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Background: Breast cancer (BC) has been reported as one of the most common cancers diagnosed in females throughout the world. Survival rate of BC patients is affected by metastasis. So, exploring its underlying mechanisms and identifying related biomarkers to monitor BC relapse/recurrence using new statistical methods is essential. This study investigated the high-dimensional gene-expression profiles of BC patients using penalized additive hazards regression models. Methods: A publicly available dataset related to the time to metastasis in BC patients (GSE2034) was used. There was information of 22 283 genes expression profiles related to 286 BC patients. Penalized additive hazards regression models with different penalties, including LASSO, SCAD, SICA, MCP and Elastic net were used to identify metastasis related genes. Results: Five regression models with penalties were applied in the additive hazards model and jointly found 9 genes including SNU13, CLINT1, MAPK9, ABCC5, NKX3-1, NCOR2, COL2A1, and ZNF219. According the median of the prognostic index calculated using the regression coefficients of the penalized additive hazards model, the patients were labeled as high/low risk groups. A significant difference was detected in the survival curves of the identified groups. The selected genes were examined using validation data and were significantly associated with the hazard of metastasis. Conclusion: This study showed that MAPK9, NKX3-1, NCOR1, ABCC5, and CD44 are the potential recurrence and metastatic predictors in breast cancer and can be taken into account as candidates for further research in tumorigenesis, invasion, metastasis, and epithelial-mesenchymal transition of breast cancer.

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“…This technology is time consuming, has high costs due to the supplements, and requires well-established protocols for standardization as maintenance is tumor type dependent. A huge advantage of this method is that tumor organoids can phenocopy the in vivo tumor characteristics thereby allowing their use for monitoring in vitro drug responses linked to genetic alterations present in the original tumor ( 55 , 74 , 75 ), which can be also correlated to the individual clinical outcome and to the response of the corresponding tumor organoids ( 74 , 76 ). However, it should be noted that next to the complexity of their establishment and manipulation, the size of organoids can largely vary thereby influencing the drug penetrance, efficiency, and reproducibility of results ( 66 , 77 ).…”

Section: Organoids Of Head and Neck Squamous Cell Carcinomamentioning

confidence: 99%

In vitro models as tools for screening treatment options of head and neck cancer

et al. 2022

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Various in vitro models using primary and established 2- and 3-dimensional cultures, multicellular tumor spheroids, standardized tumor slice cultures, tumor organoids, and microfluidic systems obtained from tumor lesions/biopsies of head and neck cancer (HNC) have been employed for exploring and monitoring treatment options. All of these in vitro models are to a different degree able to capture the diversity of tumors, recapitulate the disease genetically, histologically, and functionally and retain their tumorigenic potential upon xenotransplantation. The models were used for the characterization of the malignant features of the tumors and for in vitro screens of drugs approved for the treatment of HNC, including chemotherapy and radiotherapy as well as recently developed targeted therapies and immunotherapies, or for novel treatments not yet licensed for these tumor entities. The implementation of the best suitable model will enlarge our knowledge of the oncogenic properties of HNC, expand the drug repertoire and help to develop individually tailored treatment strategies resulting in the translation of these findings into the clinic. This review summarizes the different approaches using preclinical in vitro systems with their advantages and disadvantages and their implementation as preclinical platforms to predict disease course, evaluate biomarkers and test therapy efficacy.

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Screening of organoids derived from patients with breast cancer implicates the repressor NCOR2 in cytotoxic stress response and antitumor immunity

Cited by 23 publications

References 74 publications

Keratin-Positive Giant Cell-Rich Tumor of Bone Harboring an HMGA2::NCOR2 Fusion: Two Cases, Including a Patient With Metastatic Disease, and Review of the Literature

Keratin-Positive Giant Cell-Rich Tumor of Bone Harboring an HMGA2::NCOR2 Fusion: Two Cases, Including a Patient With Metastatic Disease, and Review of the Literature

Identification of Prognostic Biomarkers for Breast Cancer Metastasis Using Penalized Additive Hazards Regression Model

In vitro models as tools for screening treatment options of head and neck cancer

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