tbuckley/cabot-search huggingface dataset:
Biomarker Changes during 20 Years Preceding Alzheimer’s Disease
Authors: Jianping Jia, Yuye Ning, Meilin Chen, Shuheng Wang, Hao Yang, Fangyu Li, Jiayi Ding, Yan Li, Bote Zhao, Jihui Lyu, Shanshan Yang, Xin Yan, Yue Wang, Wei Qin, Qi Wang, Ying Li, Jintao Zhang, Furu Liang, Zhengluan Liao, Shan Wang
Journal: New England Journal of Medicine (2024)

Biomarker changes that occur in the period between normal cognition and the diagnosis of sporadic Alzheimer's disease have not been extensively investigated in longitudinal studies.
Biomimetic nano-chelate diethyldithiocarbamate Cu/Fe for enhanced metalloimmunity and ferroptosis activation in glioma therapy
Authors: Rui Wang, Wenqin Song, Jie Zhu, Xinyue Shao, Chenxiao Yang, Wei Xiong, Bing Wang, Pengfei Zhao, Meiwan Chen, Yongzhuo Huang
Journal: Journal of Controlled Release (2024)
Economic evaluation for medical artificial intelligence: accuracy vs. cost-effectiveness in a diabetic retinopathy screening case
Authors: Yueye Wang, Chi Liu, Wenyi Hu, Lixia Luo, Danli Shi, Jian Zhang, Qiuxia Yin, Lei Zhang, Xiaotong Han, Mingguang He
Journal: npj Digital Medicine (2024)

Abstract Artificial intelligence (AI) models have shown great accuracy in health screening. However, for real-world implementation, high accuracy may not guarantee cost-effectiveness. Improving AI’s sensitivity finds more high-risk patients but may raise medical costs while increasing specificity reduces unnecessary referrals but may weaken detection capability. To evaluate the trade-off between AI model performance and the long-running cost-effectiveness, we conducted a cost-effectiveness analysis in a nationwide diabetic retinopathy (DR) screening program in China, comprising 251,535 participants with diabetes over 30 years. We tested a validated AI model in 1100 different diagnostic performances (presented as sensitivity/specificity pairs) and modeled annual screening scenarios. The status quo was defined as the scenario with the most accurate AI performance. The incremental cost-effectiveness ratio (ICER) was calculated for other scenarios against the status quo as cost-effectiveness metrics. Compared to the status quo (sensitivity/specificity: 93.3%/87.7%), six scenarios were cost-saving and seven were cost-effective. To achieve cost-saving or cost-effective, the AI model should reach a minimum sensitivity of 88.2% and specificity of 80.4%. The most cost-effective AI model exhibited higher sensitivity (96.3%) and lower specificity (80.4%) than the status quo. In settings with higher DR prevalence and willingness-to-pay levels, the AI needed higher sensitivity for optimal cost-effectiveness. Urban regions and younger patient groups also required higher sensitivity in AI-based screening. In real-world DR screening, the most accurate AI model may not be the most cost-effective. Cost-effectiveness should be independently evaluated, which is most likely to be affected by the AI’s sensitivity.
Author Correction: An oncogenic Ezh2 mutation induces tumors through global redistribution of histone 3 lysine 27 trimethylation
Authors: George. P Souroullas, William. R Jeck, Joel. S Parker, Jeremy. M Simon, Jie-Yu Liu, Joshiawa Paulk, Jessie Xiong, Kelly. S Clark, Yuri Fedoriw, Jun Qi, Christin. E Burd, James. E Bradner, Norman. E Sharpless
Journal: Nature Medicine (2024)
Potentiating Immunogenic Cell Death in Cold Tumor with Functional Living Materials of FeAu‐Methylene Blue Composites
Authors: Tingya Wang, Yihan Wang, Tengfei Liu, Fangfang Yu, Liu Liu, Hongjie Xiong, Wenwen Xu, Xin Fan, Xiaohui Liu, Hui Jiang, Haijun Zhang, Xuemei Wang
Journal: Advanced Healthcare Materials (2024)

Low immunogenicity, absence of tumor-infiltrating lymphocytes and immunosuppressive microenvironment of immune cold tumors are the main bottlenecks leading to unfavorable prognosis. Here, an integrated tumor bioimaging and multimodal therapeutic strategy is developed, which converts immune cold into hot by modulating oxidative stress levels, enhancing photo-killing efficacy, inducing immunogenic cell death and inhibiting the immune checkpoint. On that occasion, the unique tumor microenvironment can be harnessed to biosynthesize in situ self-assembly iron complexes and fluorescent gold nanoclusters from metal ions Fe(II) and Au(III) for active targeting and real-time visualization of the tumors, simultaneously regulating reactive oxygen species levels within tumors via peroxidase-like activity. Furthermore, methylene blue (MB)-mediated photodynamic therapy promotes the release of damage-associated molecular patterns (DAMPs), which acts as in situ tumor vaccine and further induces dendritic cells maturation, augments the infiltration of antitumor T cells and significantly impedes the primary tumor growth and proliferation. More strikingly, by synergizing with the programmed cell death receptor-1 (PD-1) checkpoint inhibitor, the immunosuppressive microenvironment is remodeled and the survival time of model mice is prolonged. In summary, this paradigm utilizes the tumor-specific microenvironment to boost robust and durable systemic antitumor immunity, providing a novel opportunity for precision cancer theranostics.
Full adherence to cirrhosis quality indicators is associated with lower mortality in acute variceal bleeding: Nationwide audit
Authors: Yu Jun Wong, Margaret Teng, Alyssa Sim, Htay Myat Thet, Xuhui Teoh, Marianne Anastasia De Roza, Guan Sen Kew, Jia Hong Koh, Pooi Ling Loi, Kai Lim, Garrett Kang, Jonathan Kuang, En Xian Sarah Low, Jing Liang HO, Liu Yuan Gabriel Cher, Kenny Sze, Guan Wee Wong, Boon Yew Andrew Kwek, Wei Lyn Yang, Juan G. Abraldes, Jason Chang
Journal: Hepatology (2024)

Acute variceal bleeding (AVB) is a major complication in patients with cirrhosis. Using a nationwide AVB audit, we performed a nested cohort study to determine whether full adherence to the AVB quality indicator (QI) improves clinical outcomes in patients with cirrhosis and AVB.
Synthetic development of a broadly neutralizing antibody against snake venom long-chain α-neurotoxins
Authors: Irene S. Khalek, R. R. Senji Laxme, Yen Thi Kim Nguyen, Suyog Khochare, Rohit N. Patel, Jordan Woehl, Jessica M. Smith, Karen Saye-Francisco, Yoojin Kim, Laetitia Misson Mindrebo, Quoc Tran, Mateusz Kędzior, Evy Boré, Oliver Limbo, Megan Verma, Robyn L. Stanfield, Stefanie K. Menzies, Stuart Ainsworth, Robert A. Harrison, Dennis R. Burton, Devin Sok, Ian A. Wilson, Nicholas R. Casewell, Kartik Sunagar, Joseph G. Jardine
Journal: Science Translational Medicine (2024)

Snakebite envenoming is a major global public health concern for which improved therapies are urgently needed. The antigenic diversity present in snake venom toxins from various species presents a considerable challenge to the development of a universal antivenom. Here, we used a synthetic human antibody library to find and develop an antibody that neutralizes long-chain three-finger α-neurotoxins produced by numerous medically relevant snakes. Our antibody bound diverse toxin variants with high affinity, blocked toxin binding to the nicotinic acetylcholine receptor in vitro, and protected mice from lethal venom challenge. Structural analysis of the antibody-toxin complex revealed a binding mode that mimics the receptor-toxin interaction. The overall workflow presented is generalizable for the development of antibodies that target conserved epitopes among antigenically diverse targets, and it offers a promising framework for the creation of a monoclonal antibody–based universal antivenom to treat snakebite envenoming.
Lipid nanoparticles and siRNA targeting plasminogen provide lasting inhibition of fibrinolysis in mouse and dog models of hemophilia A
Authors: Amy W. Strilchuk, Woosuk S. Hur, Paul Batty, Yaqiu Sang, Sara R. Abrahams, Alyssa S.M. Yong, Jerry Leung, Lakmali M. Silva, Jocelyn A. Schroeder, Kate Nesbitt, Bas de Laat, Niki M. Moutsopoulos, Thomas H. Bugge, Qizhen Shi, Pieter R. Cullis, Elizabeth P. Merricks, Alisa S. Wolberg, Matthew J. Flick, David Lillicrap, Timothy C. Nichols, Christian J. Kastrup
Journal: Science Translational Medicine (2024)

Antifibrinolytic drugs are used extensively for on-demand treatment of severe acute bleeding. Controlling fibrinolysis may also be an effective strategy to prevent or lessen chronic recurring bleeding in bleeding disorders such as hemophilia A (HA), but current antifibrinolytics have unfavorable pharmacokinetic profiles. Here, we developed a long-lasting antifibrinolytic using small interfering RNA (siRNA) targeting plasminogen packaged in clinically used lipid nanoparticles (LNPs) and tested it to determine whether reducing plasmin activity in animal models of HA could decrease bleeding frequency and severity. Treatment with the siRNA-carrying LNPs reduced circulating plasminogen and suppressed fibrinolysis in wild-type and HA mice and dogs. In HA mice, hemostatic efficacy depended on the injury model; plasminogen knockdown improved hemostasis after a saphenous vein injury but not tail vein transection injury, suggesting that saphenous vein injury is a murine bleeding model sensitive to the contribution of fibrinolysis. In dogs with HA, LNPs carrying siRNA targeting plasminogen were as effective at stabilizing clots as tranexamic acid, a clinical antifibrinolytic, and in a pilot study of two dogs with HA, the incidence of spontaneous or excess bleeding was reduced during 4 months of prolonged knockdown. Collectively, these data demonstrate that long-acting antifibrinolytic therapy can be achieved and that it provides hemostatic benefit in animal models of HA.
Lipocalin-2 expression identifies an intestinal regulatory neutrophil population during acute graft-versus-host disease
Authors: Marie Czech, Sophia Schneider, Nina Peltokangas, Nadia El Khawanky, Sakhila Ghimire, Geoffroy Andrieux, Jan Hülsdünker, Máté Krausz, Michele Proietti, Lukas M. Braun, Tamina Rückert, Marlene Langenbach, Dominik Schmidt, Ina Martin, Valentin Wenger, Enrique de Vega, Eileen Haring, Mohsen Pourjam, Dietmar Pfeifer, Annette Schmitt-Graeff, Bodo Grimbacher, Konrad Aumann, Brigitte Kircher, Herbert Tilg, Manuela Raffatellu, Erik Thiele Orberg, Georg Häcker, Justus Duyster, Natalie Köhler, Ernst Holler, David Nachbaur, Melanie Boerries, Romana R. Gerner, Dominic Grün, Robert Zeiser
Journal: Science Translational Medicine (2024)

Acute graft-versus-host disease (aGVHD) is a life-threatening complication of allogeneic hematopoietic cell transplantation (allo-HCT), for which therapeutic options are limited. Strategies to promote intestinal tissue tolerance during aGVHD may improve patient outcomes. Using single-cell RNA sequencing, we identified a lipocalin-2 (LCN2)–expressing neutrophil population in mice with intestinal aGVHD. Transfer of LCN2-overexpressing neutrophils or treatment with recombinant LCN2 reduced aGVHD severity, whereas the lack of epithelial or hematopoietic LCN2 enhanced aGVHD severity and caused microbiome alterations. Mechanistically, LCN2 induced insulin-like growth factor 1 receptor (IGF-1R) signaling in macrophages through the LCN2 receptor SLC22A17, which increased interleukin-10 (IL-10) production and reduced major histocompatibility complex class II (MHCII) expression. Transfer of LCN2-pretreated macrophages reduced aGVHD severity but did not reduce graft-versus-leukemia effects. Furthermore, LCN2 expression correlated with IL-10 expression in intestinal biopsies in multiple cohorts of patients with aGVHD, and LCN2 induced IGF-1R signaling in human macrophages. Collectively, we identified a LCN2-expressing intestinal neutrophil population that reduced aGVHD severity by decreasing MHCII expression and increasing IL-10 production in macrophages. This work provides the foundation for administration of LCN2 as a therapeutic approach for aGVHD.
Author Correction: An oncogene–tumor suppressor cascade drives metastatic prostate cancer by coordinately activating Ras and nuclear factor-κB
Authors: Junxia Min, Alexander Zaslavsky, Giuseppe Fedele, Sara. K McLaughlin, Elizabeth. E Reczek, Thomas De. Raedt, Isil Guney, David. E Strochlic, Laura. E MacConaill, Rameen Beroukhim, Roderick. T Bronson, Sandra Ryeom, William. C Hahn, Massimo Loda, Karen Cichowski
Journal: Nature Medicine (2024)

In the originally published version of this article, the micrograph depicting 'small control lesion' ki67 staining shown in Fig. 1g was incorrect.
Recent Advances in Group-Based Trajectory Modeling for Clinical Research
Authors: Daniel S. Nagin, Bobby L. Jones, Jonathan Elmer
Journal: Annual Review of Clinical Psychology (2024)

Group-based trajectory modeling (GBTM) identifies groups of individuals following similar trajectories of one or more repeated measures. The categorical nature of GBTM is particularly well suited to clinical psychology and medicine, where patients are often classified into discrete diagnostic categories. This review highlights recent advances in GBTM and key capabilities that remain underappreciated in clinical research. These include accounting for nonrandom subject attrition, joint trajectory and multitrajectory modeling, the addition of the beta distribution to modeling options, associating trajectories with future outcomes, and estimating the probability of future outcomes. Also discussed is an approach to selecting the number of trajectory groups.
Prenatal Exposure to Severe Stress and the Risk of Heart Failure Up to Middle-Age
Authors: Fen Yang, Imre Janszky, Nathalie Roos, Jiong Li, Krisztina D. László
Journal: JACC Heart Failure (2024)

Prenatal stress is a potential risk factor for cardiovascular disease, but its association with heart failure (HF) is unknown. The purpose of this study was to investigate whether prenatal stress, defined as maternal bereavement, was associated with HF risk up to middle-age. This cohort study included 6,758,560 live singleton births from the Danish (1973-2016) and the Swedish (1973-2014) Medical Birth Registers. The authors retrieved information on death of the mothers' close family members (partner, older children, parents, and siblings) and offspring's HF (up to 2016 in Denmark and 2020 in Sweden) from nationwide registers. They estimated HRs and 95% CIs for HF in the offspring according to maternal bereavement. During up to 48 years of follow-up, 4,812 offspring (0.07%) had a diagnosis of HF. Maternal loss of any close family member was not associated with HF in the offspring (adjusted HR: 1.04; 95% CI: 0.88-1.23). However, the most severe forms of bereavement, ie, death of a partner or an older child (adjusted HR: 1.47; 95% CI: 1.06-2.04) and unnatural death of a relative (adjusted HR: 2.77; 95% CI: 1.49-5.17), were associated with increased risks of HF. Congenital heart disease and preterm birth contributed substantially to the association of maternal loss of a partner or older child with HF risk in the offspring. Maternal loss of a partner or older child and loss of a close relative caused by unnatural causes the year before or during pregnancy were associated with increased risk of HF in offspring.
Left Main Coronary Artery Calcium and Diabetes Confer Very-High-Risk Equivalence in Coronary Artery Calcium &gt;1,000
Authors: Alexander C. Razavi, Leslee J. Shaw, Daniel S. Berman, Matthew J. Budoff, Nathan D. Wong, Viola Vaccarino, Marly van Assen, Carlo N. De Cecco, Arshed A. Quyyumi, Anurag Mehta, Paul Muntner, Michael D. Miedema, Alan Rozanski, John A. Rumberger, Khurram Nasir, Roger S. Blumenthal, Laurence S. Sperling, Martin Bødtker Mortensen, Seamus P. Whelton, Michael J. Blaha, Omar Dzaye
Journal: JACC. Cardiovascular imaging (2024)
Lipid-Encapsulated mRNAs Encoding Complex Fusion Proteins Potentiate Antitumor Immune Responses
Authors: Casey W. Shuptrine, Yuhui Chen, Jayalakshmi Miriyala, Karen Lenz, Danielle Moffett, Thuy-Ai Nguyen, Jenn Michaux, Kristen Campbell, Connor Smith, Marc Morra, Yisel Rivera-Molina, Noah Murr, Sarah Cooper, Ashlyn McGuire, Vishruti Makani, Nathan Oien, Jeffery T. Zugates, Suresh de Silva, Taylor H. Schreiber, Seymour de Picciotto, George Fromm
Journal: Cancer Research (2024)

Lipid nanoparticle (LNP)-encapsulated mRNA has been used for in vivo production of several secreted protein classes, such as IgG, and has enabled the development of personalized vaccines in oncology. Establishing the feasibility of delivering complex multispecific modalities that require higher-order structures important for their function could help expand the use of mRNA/LNP biologic formulations. Here, we evaluated whether in vivo administration of mRNA/LNP formulations of SIRPα-Fc-CD40L and TIGIT-Fc-LIGHT could achieve oligomerization and extend exposure, on-target activity, and antitumor responses comparable with that of the corresponding recombinant fusion proteins. Intravenous infusion of the formulated LNP-encapsulated mRNAs led to rapid and sustained production of functional hexameric proteins in vivo, which increased the overall exposure relative to the recombinant protein controls by ∼28 to 140 fold over 96 hours. High concentrations of the mRNA-encoded proteins were also observed in secondary lymphoid organs and within implanted tumors, with protein concentrations in tumors up to 134-fold greater than with the recombinant protein controls 24 hours after treatment. In addition, SIRPα-Fc-CD40L and TIGIT-Fc-LIGHT mRNAs induced a greater increase in antigen-specific CD8+ T cells in the tumors. These mRNA/LNP formulations were well tolerated and led to a rapid increase in serum and intratumoral IL2, delayed tumor growth, extended survival, and outperformed the activities of benchmark mAb controls. Furthermore, the mRNA/LNPs demonstrated improved efficacy in combination with anti-PD-L1 relative to the recombinant fusion proteins. These data support the delivery of complex oligomeric biologics as mRNA/LNP formulations, where high therapeutic expression and exposure could translate into improved patient outcomes.
Impending HCC diagnosis in patients with cirrhosis after HCV cure features a natural killer cell signature
Authors: Sophie Anna Engelskircher, Po-Chun Chen, Benedikt Strunz, Carlos Oltmanns, Tijana Ristic, Solomon Owusu Sekyere, Anke R.M. Kraft, Markus Cornberg, Thomas Wirth, Bernd Heinrich, Niklas K. Björkström, Heiner Wedemeyer, Norman Woller
Journal: Hepatology (2024)

The risk of developing HCC in chronically infected patients with AQ2 HCV with liver cirrhosis is significantly elevated. This risk remains high even after a sustained virological response with direct-acting antivirals. To date, disease-associated signatures of NK cells indicating HCC development are unclear.
Systemic Biological Mechanisms of Neurocognitive Dysfunction in Long-Term Survivors of Childhood Hodgkin Lymphoma
Authors: AnnaLynn M. Williams, Wei Liu, Matthew J. Ehrhardt, Sedigheh Mirzaei Salehabadi, Angela Panoskaltsis-Mortari, Nicholas S. Phillips, Daniel A. Mulrooney, Jamie E. Flerlage, Yutaka Yasui, Deokumar Srivastava, Leslie L. Robison, Melissa M. Hudson, Kirsten K. Ness, Noah D. Sabin, Kevin R. Krull
Journal: Clinical Cancer Research (2024)

Hodgkin lymphoma (HL) survivors experience neurocognitive impairment despite receiving no central nervous system-directed therapy, though little is known about the underlying mechanisms.
Psychedelic Drugs Might Support Sexual Well-Being, Studies Find
Authors: Emily Harris
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Combined Effects of Polystyrene Nanosphere and Homosolate Exposures on Estrogenic End Points in MCF-7 Cells and Zebrafish
Authors: Rongyi Ye, Zhiming Li, Hongyi Xian, Yizhou Zhong, Boxuan Liang, Yuji Huang, Da Chen, Mingzhu Dai, Shuqin Tang, Jie Guo, Ruobing Bai, Yu Feng, Zhenguo Chen, Xingfen Yang, Zhenlie Huang
Journal: Environmental Health Perspectives (2024)

Micro- and nanoplastics (MNPs) and homosalate (HMS) are ubiquitous emerging environmental contaminants detected in human samples. Despite the well-established endocrine-disrupting effects (EDEs) of HMS, the interaction between MNPs and HMS and its impact on HMS-induced EDEs remain unclear.
Coarse Particulate Matter and Markers of Inflammation and Coagulation in the Multi-Ethnic Study of Atherosclerosis (MESA) Population: A Repeat Measures Analysis
Authors: Meredith Pedde, Timothy V. Larson, Jennifer D’Souza, Adam A. Szpiro, Itai Kloog, Lynda D. Lisabeth, David Jacobs, Lianne Sheppard, Matthew Allison, Joel D. Kaufman, Sara D. Adar
Journal: Environmental Health Perspectives (2024)

In contrast to fine particles, less is known of the inflammatory and coagulation impacts of coarse particulate matter (PM10–2.5, particulate matter with aerodynamic diameter ≤10μm and>2.5μm). Toxicological research suggests that these pathways might be important processes by which PM10–2.5 impacts health, but there are relatively few epidemiological studies due to a lack of a national PM10–2.5 monitoring network.
Truth-telling in dermatology: historical perspective and modern challenges to breaking bad news
Authors: Emily R. Gordon, Megan H. Trager, Oluwaseyi Adeuyan, Caroline Chen, Brigit A. Lapolla, Celine M. Schreidah, Cori Salvit, Douglas J. Koo, Larisa J. Geskin
Journal: Journal of the American Academy of Dermatology (2024)
Use of Efficiency Frontiers to Align Prices and Clinical Benefits of Biologic Therapies for Plaque Psoriasis
Authors: Alexander C. Egilman, Aaron S. Kesselheim, Jerry Avorn, Adam J. N. Raymakers, Benjamin N. Rome
Journal: JAMA Dermatology (2024)

The US lacks a systematic approach for aligning drug prices with clinical benefit, and traditional cost-effectiveness analysis (CEA) faces political obstacles. The efficiency frontier (EF) method offers policymakers an alternative approach.
Selective CDK7 Inhibition Suppresses Cell Cycle Progression and MYC Signaling While Enhancing Apoptosis in Therapy-resistant Estrogen Receptor–positive Breast Cancer
Authors: Cristina Guarducci, Agostina Nardone, Douglas Russo, Zsuzsanna Nagy, Capucine Heraud, Albert Grinshpun, Qi Zhang, Allegra Freelander, Mathew Joseph Leventhal, Avery Feit, Gabriella Cohen Feit, Ariel Feiglin, Weihan Liu, Francisco Hermida-Prado, Nikolas Kesten, Wen Ma, Carmine De Angelis, Antonio Morlando, Madison O'Donnell, Sergey Naumenko, Shixia Huang, Quang-Dé Nguyen, Ying Huang, Luca Malorni, Johann S. Bergholz, Jean J. Zhao, Ernest Fraenkel, Elgene Lim, Rachel Schiff, Geoffrey I. Shapiro, Rinath Jeselsohn
Journal: Clinical Cancer Research (2024)

Resistance to endocrine therapy (ET) and CDK4/6 inhibitors (CDK4/6i) is a clinical challenge in estrogen receptor (ER)-positive (ER+) breast cancer. Cyclin-dependent kinase 7 (CDK7) is a candidate target in endocrine-resistant ER+ breast cancer models and selective CDK7 inhibitors (CDK7i) are in clinical development for the treatment of ER+ breast cancer. Nonetheless, the precise mechanisms responsible for the activity of CDK7i in ER+ breast cancer remain elusive. Herein, we sought to unravel these mechanisms.