tbuckley/cabot-search huggingface dataset:
Epidemiology of human metapneumovirus among children with severe or very severe pneumonia in high pneumonia burden settings: the PERCH study experience
Authors: Ryo Miyakawa, Haijun Zhang, W. Abdullah Brooks, Christine Prosperi, Henry C. Baggett, Daniel R. Feikin, Laura L. Hammitt, Stephen R.C. Howie, Karen L. Kotloff, Orin S. Levine, Shabir A. Madhi, David R. Murdoch, Katherine L. O'Brien, J. Anthony G. Scott, Donald M. Thea, Martin Antonio, Juliet O. Awori, Charatdao Bunthi, Amanda J. Driscoll, Bernard Ebruke, Nicholas S. Fancourt, Melissa M. Higdon, Ruth A. Karron, David P. Moore, Susan C. Morpeth, Justin M. Mulindwa, Daniel E. Park, Mohammed Ziaur Rahman, Mustafizur Rahman, Rasheed A. Salaudeen, Pongpun Sawatwong, Phil Seidenberg, Samba O. Sow, Milagritos D. Tapia, Maria Deloria Knoll
Journal: Clinical Microbiology and Infection (2024)

ObjectivesAfter respiratory syncytial virus (RSV), human metapneumovirus (hMPV) was the second-ranked pathogen attributed to severe pneumonia in the PERCH study. We sought to characterize hMPV-positive cases in high burden settings, which have limited data, by comparing to RSV-positive and other cases.MethodsChildren aged 1-59 months hospitalized with suspected severe pneumonia and age/season-matched community controls in seven African and Asian countries had nasopharyngeal/oropharyngeal swabs tested by multiplex PCR for 32 respiratory pathogens, among other clinical and lab assessments at admission. Odds ratios adjusted for age and site (aOR) were calculated using logistic regression. Etiologic probability was estimated using Bayesian nested partial latent class analysis. Latent class analysis identified syndromic constellations of clinical characteristics.ResultsHMPV was detected more frequently among cases (267/3887, 6.9%) than controls (115/4976, 2.3%), among cases with pneumonia chest X-ray findings (8.5%) than without (5.5%), and among controls with respiratory tract illness (3.8%) than without (1.8%; all p≤0.001). HMPV-positive cases were negatively associated with the detection of other viruses (aOR=0.18), especially RSV (aOR=0.11; all p<0.0001), and positively associated with the detection of bacteria (aORs 1.77, p=0.03). No single clinical syndrome distinguished hMPV-positive from other cases. Among hMPV-positive cases, 65.2% were aged <1 year and 27.5% had pneumonia danger signs; positive predictive value was 74.5%; mortality was 3.9%, similar to RSV-positive (2.4%) and lower than other cases (9.6%).ConclusionsHMPV-associated severe pediatric pneumonia in high burden settings was predominantly in young infants and clinically indistinguishable from RSV. HMPV-positives had low case fatality, similar to that in RSV-positives.
A mutant BCL11B-N440K protein interferes with BCL11A function during T lymphocyte and neuronal development
Authors: Kazuki Okuyama, Motoi Yamashita, Artemis Koumoundourou, Christoph Wiegreffe, Michiko Ohno-Oishi, Samuel J. H. Murphy, Xin Zhao, Hideyuki Yoshida, Takashi Ebihara, Naoko Satoh-Takayama, Satoshi Kojo, Hiroshi Ohno, Tomohiro Morio, Yibo Wu, Jennifer Puck, Hai-Hui Xue, Stefan Britsch, Ichiro Taniuchi
Journal: Nature Immunology (2024)
Recapitulating the adenoma–carcinoma sequence by selection of four spontaneous oncogenic mutations in mismatch-repair-deficient human colon organoids
Authors: Tomohiro Mizutani, Matteo Boretto, Sangho Lim, Jarno Drost, Diego Montiel González, Rurika Oka, Maarten H. Geurts, Harry Begthel, Jeroen Korving, Johan H. van Es, Ruben van Boxtel, Hans Clevers
Journal: Nature Cancer (2024)

Carcinogenesis results from the sequential acquisition of oncogenic mutations that convert normal cells into invasive, metastasizing cancer cells. Colorectal cancer exemplifies this process through its well-described adenoma-carcinoma sequence, modeled previously using clustered regularly interspaced short palindromic repeats (CRISPR) to induce four consecutive mutations in wild-type human gut organoids. Here, we demonstrate that long-term culture of mismatch-repair-deficient organoids allows the selection of spontaneous oncogenic mutations through the sequential withdrawal of Wnt agonists, epidermal growth factor (EGF) agonists and the bone morphogenetic protein (BMP) antagonist Noggin, while TP53 mutations were selected through the addition of Nutlin-3. Thus, organoids sequentially acquired mutations in AXIN1 and AXIN2 (Wnt pathway), TP53, ACVR2A and BMPR2 (BMP pathway) and NRAS (EGF pathway), gaining complete independence from stem cell niche factors. Quadruple-pathway (Wnt, EGF receptor, p53 and BMP) mutant organoids formed solid tumors upon xenotransplantation. This demonstrates that carcinogenesis can be recapitulated in a DNA repair-mutant background through in vitro selection that targets four consecutive cancer pathways.
Global Meningococcal Initiative: Insights on antibiotic resistance, control strategies and advocacy efforts in Western Europe
Authors: Ray Borrow, Helen Campbell, Dominique A Caugant, Abdessalam Cherkaoui, Heike Claus, Ala-Eddine Deghmane, Ener Cagri Dinleyici, Lee H Harrison, William P Hausdorff, Paula Bajanca-Lavado, Corinne Levy, Wesley Mattheus, Claudia Mikula-Pratschke, Paula Mölling, Marco Ap Sáfadi, Vinny Smith, Nina M van Sorge, Paola Stefanelli, Muhamed-Kheir Taha, Maija Toropainen, Georgina Tzanakaki, Julio Vázquez
Journal: Journal of Infection (2024)
Hepatocyte-specific SLC27A4 deletion ameliorates nonalcoholic fatty liver disease in mice via suppression of phosphatidylcholine-mediated PXR activation
Authors: Chuangpeng Shen, Zhisen Pan, Wenmin Xie, Jian Zhao, Deyu Miao, Ling Zhao, Min Liu, Yanhua Zhong, Chong Zhong, Frank J. Gonzalez, Wei Wang, Yong Gao, Changhui Liu
Journal: Metabolism (2024)
Referral, monitoring, and factors associated with non-referral of chronic kidney disease in Germany: a nationwide, retrospective cohort study
Authors: Friedrich A von Samson-Himmelstjerna, Edgar Steiger, Benedikt Kolbrink, Hauke S Wülfrath, Thomas Czihal, Roland Schmitt, Dominik von Stillfried, Kevin Schulte
Journal: The Lancet Regional Health - Europe (2024)
Alzheimer Disease—What’s in a Name?
Authors: Ronald C. Petersen, Elizabeth Mormino, Julie A. Schneider
Journal: JAMA Neurology (2024)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast JAMA+ AI Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
Vagal innervation limits brain injury by inhibiting gut-selective integrin-mediated intestinal immunocyte migration in intracerebral hemorrhage
Authors: Peiji Fu, Yan Zong, Yinming Dai, Li Zhu, Shuai Chen, Yousef Rastegar-Kashkooli, Junmin Wang, Jiewen Zhang, Jian Wang, Chao Jiang
Journal: Theranostics (2024)

: The vagus nerve, which connects the brain and gastrointestinal tract, helps to maintain immune balance in the intestines. Gut-specific integrins, on the other hand, help to keep immune cells in the intestines. Since immune cells from outside the intestines can significantly affect the outcome of strokes, we investigated how immune cells from the intestines affect the immune response in the brain during intracerebral hemorrhage (ICH).
Circular RNA SCMH1 suppresses KMO expression to inhibit mitophagy and promote functional recovery following stroke
Authors: Yu Wang, Ying Bai, Yang Cai, Yuan Zhang, Ling Shen, Wen Xi, Zhongqiu Zhou, Lian Xu, Xue Liu, Bing Han, Honghong Yao
Journal: Theranostics (2024)

Metabolic dysfunction is one of the key pathological events after ischemic stroke. Disruption of cerebral blood flow impairs oxygen and energy substrate delivery, leading to mitochondrial oxidative phosphorylation dysfunction and cellular bioenergetic stress. Investigating the effects of circSCMH1, a brain repair-related circular RNA, on metabolism may identify novel therapeutic targets for stroke treatment.
Emerging advanced approaches for liquid biopsy: <i>in situ</i> nucleic acid assays of extracellular vesicles
Authors: Dongli Wang, Ye Shen, Hui Qian, Jiajia Jiang, Wenrong Xu
Journal: Theranostics (2024)

Extracellular vesicles (EVs) have emerged as valuable biomarkers in liquid biopsies owing to their stability, accessibility, and ability to encapsulate nucleic acids. The majority of existing methodologies for detecting EV nucleic acid biomarkers require the lysis of EVs to extract DNA or RNA. This process is labor-intensive and may lead to the loss and degradation of nucleic acids. However, the emerging field of
Multifunctional injectable hydrogel system as a mild photothermal-assisted therapeutic platform for programmed regulation of inflammation and osteo-microenvironment for enhanced healing of diabetic bone defects <i>in situ</i>
Authors: Yufan Zhu, Huifan Liu, Ping Wu, Yun Chen, Zhouming Deng, Lin Cai, Minhao Wu
Journal: Theranostics (2024)

Factor-free biomaterial scaffolds play an increasingly important role in promoting
[<sup>18</sup>F]AlF-NOTA-pentixather PET/CT of CXCR4 in patients with suspected primary hyperaldosteronism
Authors: Limeng He, Yan Yang, Xu Cao, Xianjun Zhu, Nan Liu, Xiaoyuan Chen, Jingjing Zhang, Wei Zhang
Journal: Theranostics (2024)

Distinguishing unilateral aldosterone-producing adenomas (APA) from idiopathic hyperaldosteronism (IHA), nonfunctional adrenal adenoma (NFA), and pheochromocytoma (PHEO) within primary aldosteronism (PA) presents a significant challenge. Studies have demonstrated high levels of chemokine receptor (CXCR) 4 expression in APA, thereby validating the use of
Gut microbiota depletion and FXR inhibition exacerbates zonal hepatotoxicity of sunitinib
Authors: Qi Zhao, Yingmei Lu, Jingyi Duan, Dan Du, Qianlun Pu, Fei Li
Journal: Theranostics (2024)

Rationale: Sunitinib is a small-molecule tyrosine kinase inhibitor associated with the side-effect of liver injury. The impaired cell type in liver and the hepatotoxicity mechanisms is still unclear. Methods: Spatial metabolomics, transmission electron microscopy, immunofluorescence co-staining, and isolation of bile duct cells and liver sinusoidal endothelial cells (LSECs) were used to evaluate the zonated hepatotoxicity of sunitinib. Farnesoid X receptor (FXR) conditional knockout mice, metagenomics analysis, bacteria clearance, bacterial culture, Parabacteroides distasonis and 3-oxolithocholic acid supplementation were used to evaluate the hepatotoxicity mechanisms of sunitinib. Results: Phenotype analysis found that hepatic autophagy, apoptosis, and mitochondrial injury were observed in vivo or in vitro after sunitinib treatment. By using spatial metabolomics and isolation of bile duct cells and LSECs, the zonated drug toxicity was observed around the portal vein. Hepatocytes, bile duct cells, and LSECs were damaged after sunitinib treatment. FXR inhibition and gut microbiota depletion aggravated sunitinib-induced liver injury. For diurnal variation, sunitinib-induced liver injury was enhanced at night compared with that at day, and FXR and gut microbiota participated in circadian rhythmic hepatotoxicity induced by sunitinib. Conclusions: Our data suggested activation of FXR and Parabacteroides distasonis supplementation may be used to improve sunitinib-induced hepatotoxicity.
A CIA strategy with eminent drug-loading capacities for tumor ferroptosis-gas synergistic therapy
Authors: Jiaoyang Zhu, Lin Huang, Jing Yang, Zongheng Li, Lihe Wu, Wei Xiong, Jie Feng, Chenggong Yan, Chaomin Chen, Yan Li, Zheyu Shen
Journal: Theranostics (2024)

: A common challenge of drug loading and delivery using magnetic resonance imaging (MRI) contrast agents (CAs) is the tendency of aggregation and precipitation at high drug loading conditions. Herein, we propose a generic strategy of controlled ideal aggregation (CIA) to restrict the tendency.
Branched-chain amino acids deficiency promotes diabetic cardiomyopathy by activating autophagy of cardiac fibroblasts
Authors: Ze-Yu Zhou, Kai Song, Zhi-Yan Liu, Yu-Fan Ke, Yan Shi, Ke Cai, Rui Zhao, Xin Sun, Hui Tao, Jian-Yuan Zhao
Journal: Theranostics (2024)

Rationale: More than half of the patients with type II diabetes mellitus (T2D) develop diabetic cardiomyopathy (DCM). Glycemic control alone cannot effectively prevent or alleviate DCM. Methods: Herein, we concentrated on the variations in levels of metabolites between DCM and T2D patients without cardiomyopathy phenotype. In high-fat diet/low-dose streptozotocin-induced T2D and leptin receptor-deficient diabetic mouse models, we investigated the effect of altering branched-chain amino acids (BCAAs) levels on DCM. Results: We discovered that the levels of plasma BCAAs are notably lower in 15 DCM patients compared to 19 T2D patients who do not exhibit cardiomyopathy phenotype, using nuclear magnetic resonance analysis. This finding was further validated in two additional batches of samples, 123 DCM patients and 129 T2D patients based on the BCAA assay kit, and 30 DCM patients and 30 T2D patients based on the LC-MS/MS method, respectively. Moreover, it is verified that BCAA deficiency aggravated, whereas BCAA supplementation alleviated cardiomyopathy phenotypes in diabetic mice. Furthermore, BCAA deficiency promoted cardiac fibroblast activation by stimulating autophagy in DCM mice. Mechanistically, BCAA deficiency activated autophagy via the AMPK-ULK1 signaling pathway in cardiac fibroblasts. Using pharmacological approaches, we validated our findings that autophagy inhibition relieved, whereas autophagy activation aggravated, DCM phenotypes. Conclusions: Taken together, we describe a novel perspective wherein BCAA supplementation may serve as a potential therapeutic agent to mitigate DCM and fibrosis. Our findings provide insights for the development of preventive measures for DCM.
SPHK1 promotes HNSCC immune evasion by regulating the MMP1-PD-L1 axis
Authors: Qi Fang, Xiao Chen, Fei Cao, Pengfei Xu, Zheng Zhao, Roubin Lin, Di Wu, Wuguo Deng, Xuekui Liu
Journal: Theranostics (2024)

Rationale: Immune checkpoint inhibitors (ICIs) have demonstrated significant efficacy against head and neck squamous cell carcinoma (HNSCC), but their overall response rate (ORR) remains limited. Previous studies have highlighted the crucial role of sphingosine kinases (SPHKs) in the tumor microenvironment (TME); however, their function in immunotherapy remains unclear. Methods: We conducted comprehensive bioinformatics analysis, functional studies, and clinical validation, to investigate the role of SPHK1 in the immunology of HNSCC. Results: Functionally, SPHK1 significantly promoted tumor growth by inhibiting anti-tumor immunity in immune-competent HNSCC mouse models and tumor-T cell co-cultures. Mechanistic analysis revealed that SPHK1 regulated matrix metalloproteinase-1 (MMP1) expression via the MAPK1 pathway, which subsequently influenced tumor programmed cell death ligand 1 (PD-L1) expression. Furthermore, SPHK1 and MMP1 could predict the efficacy of programmed cell death 1 monoclonal antibody (PD-1 mAb) immunotherapy in HNSCC and were independent risk factors for survival in patients with HNSCC. Conclusion: Our study reveals a novel role for SPHK1 in mediating immune evasion in HNSCC through the regulation of the MMP1-PD-L1 axis. We identified SPHK1 and MMP1 as predictive biomarkers for the therapeutic response to PD-1 mAb and provided new therapeutic targets for patients with HNSCC.
Preclinical evaluation of radiolabeled tissue factor-targeted peptide for theranostics of hepatocellular carcinoma post percutaneous ethanol injection
Authors: Buchuan Zhang, Pei Wang, Qiaorong Chen, Yilin Yang, Feng Xiong, Guangfa Bao, Jingfei Yang, Ziqiang Wang, Huimin Zhou, Shuang Song, Sijuan Zou, Dong-Hyun Kim, Bo Yu, Xiaohua Zhu
Journal: Theranostics (2024)

Tissue factor (TF) initiates local blood clotting and infiltration of tumor-associated macrophages, leading to tumor recurrence post-local ablation. Our study addressed inefficient cancer cell killing and immunosuppressive macrophage infiltration after percutaneous ethanol injection (PEI) in hepatocellular carcinoma (HCC). We evaluated the feasibility of
Development of machine-learning-driven signatures for diagnosing and monitoring therapeutic response in major depressive disorder using integrated immune cell profiles and plasma cytokines
Authors: Shen He, Faming Zhao, Guangqiang Sun, Yue Shi, Tianlun Xu, Yu Zhang, Siyuan Li, Linna Zhang, Xingkun Chu, Chen Du, Dabing Yang, Jing Zhang, Changrong Ge, Jingjing Huang, Zuoquan Xie, Huafang Li
Journal: Theranostics (2024)

Diagnosis and treatment efficacy of major depressive disorder (MDD) currently lack stable and reliable biomarkers. Previous research has suggested a potential association between immune cells, cytokines, and the pathophysiology and treatment of MDD.
Revolutionizing cancer treatment: the emerging potential and potential challenges of <i>in vivo</i> self-processed CAR cell therapy
Authors: Ruijie Lv, Yanting Guo, Weici Liu, Guangjian Dong, Xiangyin Liu, Caihui Li, Yi Ren, Zipeng Zhang, Shi-Yong Neo, Wenjun Mao, Jing Wu
Journal: Theranostics (2024)

Chimeric antigen receptor (CAR) cell immunotherapies, including CAR-T, CAR-Macrophages, CAR-Natural Killer, CAR-γδ T, etc., have demonstrated significant advancements in the treatment of both hematologic malignancies and solid tumors. Despite the notable successes of traditional CAR cell manufacturing, its application remains constrained by the complicated production process and expensive costs. Consequently, efforts are focused on streamlining CAR cell production to enhance efficacy and accessibility. Among numerous proposed strategies, direct
ZNF131-BACH1 transcriptionally accelerates RAD51-dependent homologous recombination repair and therapy-resistance of non-small-lung cancer cells by preventing their degradation from CUL3
Authors: Mingwei Fan, Quanbo Liu, Xiaowen Ma, Yufeng Jiang, Yilong Wang, Shuting Jia, Yingtong Nie, Ruoyi Deng, Pengchong Zhou, Shuyu Zhang, Siyu Jiang, Mengyao Guan, Yuekang Hou, Yuan Miao, Yong Zhang, Xiupeng Zhang
Journal: Theranostics (2024)

Rationale: Both bulk RNA-sequencing and GEO database upon chemotherapy to non-small cell lung cancer (NSCLC) cells reveal that ZNF131 (Zinc Finger Protein 131) maybe a crucial transcriptional factor involved. However, it is a recently discovered protein with largely unexplored expression patterns and biological functions. Methods: Bioinformatics analyses and immunohistochemistry staining were assessed to detect both mRNA and protein levels of ZNF131 in NSCLC specimens and cell lines. Next, colony formation assay, MTT assay, EdU assay, transwell assay, flow cytometric analysis, sphere formation assay, western blotting analysis, mouse xenograft model analysis, immunofluorescence assay, and reverse transcriptase-polymerase chain reaction were performed to investigate the effect of ZNF131 interaction on proliferation, invasion, stemness, chemotherapy sensitivity. RNA-sequencing assay, RNA-microarray, and ChIP-sequencing assay were used to identify candidate downstream target genes. Further, liquid chromatography-tandem mass spectrometry analysis, GST pull-down assay, and immunoprecipitation assays were performed to evaluate the interactions between ZNF131, BACH1, and CUL3. Results: ZNF131 was elevated in NSCLC specimens and cell lines, which significantly correlates with advanced TNM stage and poor prognosis in NSCLC patients. ZNF131 overexpression promotes NSCLC cell proliferation, invasion, and stemness both in vitro and in vivo. ZNF131 appears to target the RAD51 gene within a well-defined region (-668bp to -403bp) of the RAD51 promoter. ZNF131 contributes to RAD51-dependent homologous recombination (HR), primarily through its Zinc Finger and BTB domains. ZNF131-BACH1 interaction, mediated by their respective BTB domains, enhances the stability of both proteins, effectively preventing their ubiquitin-mediated degradation by CUL3. The ZNF131-BACH1 partnership significantly amplifies RAD51-dependent HR, resulting in expedited resistance to both radiotherapy and chemotherapy in NSCLC patients. Desoxyrhaponticin was shown to halt NSCLC progression and orchestrate a synergistic effect together with chemotherapy at least partially by targeting ZNF131. Conclusions: Our findings indicate that ZNF131 exhibits heightened expression in NSCLC, driving essential processes such as proliferation, invasion, and stemness by transcriptionally activating RAD51. The ZNF131-BACH1 interaction serves as a crucial enhancer, further boosting RAD51 transcription and ultimately accelerating therapy resistance in NSCLC.
Deciphering the effects of radiopharmaceutical therapy in the tumor microenvironment of prostate cancer: an in-silico exploration with spatial transcriptomics
Authors: Jimin Hong, Sungwoo Bae, Lara Cavinato, Robert Seifert, Marc Ryhiner, Axel Rominger, Kjell Erlandsson, Moses Wilks, Marc Normandin, Georges El-Fakhri, Hongyoon Choi, Kuangyu Shi
Journal: Theranostics (2024)

Radiopharmaceutical therapy (RPT) is an emerging prostate cancer treatment that delivers radiation to specific molecules within the tumor microenvironment (TME), causing DNA damage and cell death. Given TME heterogeneity, it's crucial to explore RPT dosimetry and biological impacts at the cellular level. We integrated spatial transcriptomics (ST) with computational modeling to investigate the effects of RPT targeting prostate-specific membrane antigen (PSMA), fibroblast activation protein (FAP), and gastrin-releasing peptide receptor (GRPR) each labelled with beta-emitting lutetium-177 (
Silencing of METTL3 effectively hinders invasion and metastasis of prostate cancer cells: Erratum
Authors: Yabing Chen, Chun Pan, Xiaotong Wang, Dihui Xu, Yuhan Ma, Jianhang Hu, Peilin Chen, Zou Xiang, Qiu Rao, Xiaodong Han
Journal: Theranostics (2024)

[This corrects the article DOI: 10.7150/thno.61178.].
High caloric intake improves neuronal metabolism and functional hyperemia in a rat model of early AD pathology
Authors: Dustin Loren V Almanza, Margaret M Koletar, Aaron Y Lai, Wilfred W Lam, Lewis Joo, Mary E Hill, Greg J Stanisz, JoAnne McLaurin, Bojana Stefanovic
Journal: Theranostics (2024)

While obesity has been linked to both increased and decreased rate of cognitive decline in Alzheimer's Disease (AD) patients, there is no consensus on the interaction between obesity and AD.
Targeting Noncoding <i>cis</i>-Regulatory Elements for Cancer Therapy in the Context of the 3D Genome
Authors: Kailong Li, Gong-Hong Wei, Yuxin Yin, Jiawen Feng
Journal: Cancer Discovery (2024)

Significant efforts have been made to identify and validate oncoproteins and ncRNAs as therapeutic targets for cancer therapy; however, emerging observations suggest that noncoding cis-regulatory elements, which orchestrate the 3D organization of the genome and thus the transcriptional landscape, are potential therapeutic targets as well. In this commentary, we envisage that further efforts to decipher the noncoding cis-regulatory code and performing systematic surveys of functional noncoding cis-regulatory elements and recurrent 3D genome alterations in both cancerous and nonmalignant cells within tumor tissues will pave the way to the development of novel therapeutic strategies.