The Journal of Clinical Investigation最新文献

{"title":"A predictive endocrine resistance index accurately stratifies luminal breast cancer treatment responders and non-responders.","authors":"Guokun Zhang,Vindi Jurinovic,Stephan Bartels,Matthias Christgen,Henriette Christgen,Leonie Donata Kandt,Lidiya Mishieva,Hua Ni,Mieke Raap,Janin Klein,Anna-Lena Katzke,Winfried Hofmann,Doris Steinemann,Ronald E Kates,Oleg Gluz,Monika Graeser,Sherko Kuemmel,Ulrike Nitz,Christoph Plass,Ulrich Lehmann,Christine Zu Eulenburg,Ulrich Mansmann,Clarissa Gerhauser,Nadia Harbeck,Hans H Kreipe","doi":"10.1172/jci177813","DOIUrl":"https://doi.org/10.1172/jci177813","url":null,"abstract":"BACKGROUNDEndocrine therapy (ET) with tamoxifen (TAM) or aromatase inhibitors (AI) is highly effective against hormone receptor (HR) positive early breast cancer (BC), but resistance remains a major challenge. The primary objectives of our study were to understand the underlying mechanisms of primary resistance and to identify potential biomarkers.METHODSWe selected >800 patients in three sub-cohorts (Discovery, N=364, matched pairs), Validation 1, N=270, Validation 2, N= 176) of the West German Study Group (WSG) Adjuvant Dynamic marker-Adjusted Personalized Therapy (ADAPT) trial who underwent short-term pre-operative TAM or AI treatment. Treatment response was assessed by immunohistochemical labeling of proliferating cells with Ki67 before and after ET. We performed comprehensive molecular profiling, including targeted next-generation sequencing (NGS) and DNA methylation analysis using EPIC arrays, on post-treatment tumor samples.RESULTSTP53 mutations were strongly associated with primary resistance to both TAM and AI. In addition, we identified distinct DNA methylation patterns in resistant tumors, suggesting alterations in key signaling pathways and tumor microenvironment composition. Based on these findings and patient age, we developed the Predictive Endocrine ResistanCe Index (PERCI). PERCI accurately stratified responders and non-responders in both treatment groups in all three sub-cohorts and predicted progression-free survival in an external validation cohort and in the combined sub-cohorts.CONCLUSIONOur results highlight the potential of PERCI to guide personalized endocrine therapy and improve patient outcomes.TRIAL REGISTRATIONWSG-ADAPT, ClinicalTrials.gov NCT01779206, Registered 2013-01-25, retrospectively registered.","PeriodicalId":520097,"journal":{"name":"The Journal of Clinical Investigation","volume":"114 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144701099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inverted chimeric RNAi molecules synergistically co-target MYC and KRAS in KRAS-driven cancers.","authors":"Yogitha S Chareddy,Hayden P Huggins,Snehasudha S Sahoo,Lyla Stanland,Christina Gutierrez-Ford,Kristina M Whately,Lincy Edatt,Salma H Azam,Matthew C Fleming,Jonah Im,Alessandro Porrello,Imani Simmons,Jillian L Perry,Albert A Bowers,Martin Egli,Chad V Pecot","doi":"10.1172/jci187204","DOIUrl":"https://doi.org/10.1172/jci187204","url":null,"abstract":"Mutant KRAS has been implicated in driving a quarter of all cancer types. Although inhibition of the KRASG12C mutant protein has shown clinical promise, there is still a need for therapies that overcome resistance and target non-KRASG12C mutations. KRAS activates downstream MYC, which is also a challenging-to-drug oncoprotein. We have developed an \"inverted\" RNAi molecule with the passenger strand of a MYC-targeting siRNA fused to the guide strand of a KRAS-targeting siRNA. The chimeric molecule simultaneously inhibits KRAS and MYC, showing marked improvements in efficacy beyond the individual siRNA components. This effect is mediated by 5'-dT overhangs following endosomal metabolism. The synergistic RNAi activity led to a >10-40-fold improvement in inhibiting cancer viability in vitro. When conjugated to an epidermal growth factor receptor (EGFR)-targeting ligand, the chimeric siRNA was delivered to and internalized by tumor cells. As compared with individual targeting siRNAs, the chimeric design resulted in considerably improved metabolic stability in tumors, enhanced silencing of both oncogenes, and reduced tumor progression in multiple cancer models. This inverted chimeric design establishes proof-of-concept for ligand-directed, dual-silencing of KRAS and MYC in cancer and constitutes an innovative molecular strategy for co-targeting any two genes of interest, which has broad implications.","PeriodicalId":520097,"journal":{"name":"The Journal of Clinical Investigation","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144777941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Coenzyme A protects against ferroptosis via CoAlation of mitochondrial thioredoxin reductase.","authors":"Chao-Chieh Lin,Yi-Tzu Lin,Ssu-Yu Chen,Yasaman Setayeshpour,Yubin Chen,Denise E Dunn,Taylor Nguyen,Alexander A Mestre,Adrija Banerjee,Lalitha Guruprasad,Erik J Soderblom,Guo-Fang Zhang,Chen-Yong Lin,Valeriy Filonenko,Suh Young Jeong,Scott R Floyd,Susan J Hayflick,Ivan Gout,Jen-Tsan Chi","doi":"10.1172/jci190215","DOIUrl":"https://doi.org/10.1172/jci190215","url":null,"abstract":"The cystine-xCT transporter-glutathione (GSH)-GPX4 axis is the canonical pathway protecting cells from ferroptosis. While GPX4-targeting ferroptosis-inducing compounds (FINs) act independently of mitochondria, xCT-targeting FINs require mitochondrial lipid peroxidation, though the mechanism remains unclear. Since cysteine is also a precursor for coenzyme A (CoA) biosynthesis, here, we demonstrated that CoA supplementation selectively prevented ferroptosis triggered by xCT inhibition by regulating the mitochondrial thioredoxin system. Our data showed that CoA regulated the in vitro enzymatic activity of mitochondrial thioredoxin reductase (TXNRD2) by covalently modifying the thiol group of cysteine (CoAlation) on Cys-483. Replacing Cys-483 with alanine on TXNRD2 abolished its enzymatic activity and ability to protect cells against ferroptosis. Targeting xCT to limit cysteine import and, therefore, CoA biosynthesis reduced CoAlation on TXNRD2. Furthermore, the fibroblasts from patients with disrupted CoA metabolism demonstrated increased mitochondrial lipid peroxidation. In organotypic brain slice cultures, inhibition of CoA biosynthesis led to an oxidized thioredoxin system, increased mitochondrial lipid peroxidation, and loss of cell viability, which were all rescued by ferrostatin-1. These findings identified CoA-mediated post-translational modification to regulate the thioredoxin system as an alternative ferroptosis protection pathway with potential clinical relevance for patients with disrupted CoA metabolism.","PeriodicalId":520097,"journal":{"name":"The Journal of Clinical Investigation","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144684167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gene-environment interactions modulate the phenotypic severity in mouse models of congenital craniofacial syndromes.","authors":"Sharien Fitriasari,Roberta Fiorino,Thoa Hk Truong,Mary C McKinney,Jill Dixon,Michael J Dixon,Paul A Trainor","doi":"10.1172/jci181705","DOIUrl":"https://doi.org/10.1172/jci181705","url":null,"abstract":"Birth defects are the leading cause of infant mortality, and most inborn errors of development are multifactorial in origin, resulting from complex gene-environment interactions. Defining specific gene-environment interactions in the etiology and pathogenesis of congenital disorders is critically needed in the absence of genotype-phenotype correlation but is challenging. This is particularly true for congenital craniofacial anomalies, which account for approximately one-third of all birth defects, as they typically exhibit considerable inter-familial and intra-familial variability. A classic example of this is Treacher Collins Syndrome (TCS), which, although primarily caused by mutations in TCOF1, is characterized by considerable variability in the severity of mandibulofacial dysostosis. Here, we describe the genetic and environmental factors with converging effects that mechanistically contribute to the etiology and pathogenesis of craniofacial variation in this rare congenital disorder. We discovered in Tcof1+/- mouse models of TCS, that the combination of different endogenous levels of Tcof1/Treacle protein and reactive oxygen species (ROS) within distinct genetic backgrounds correlates with TCS phenotype severity. Furthermore, geometric morphometric analyses revealed that genotype largely determines the craniofacial shape, but redox status determines the size of individual bones. Taken together, our results highlight the roles of ROS and genomic instability in modulating the variability and phenotypic severity of craniofacial anomalies.","PeriodicalId":520097,"journal":{"name":"The Journal of Clinical Investigation","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144684380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pulmonary fibroblast-derived stem cell factor promotes neutrophilic asthma by augmenting IL-17A production from ILC3s.","authors":"Jheng-Syuan Shao,Alan C Lai,Wei-Chang Huang,Ko-Chien Wu,Po-Yu Chi,Yao-Ming Chang,Ya-Jen Chang","doi":"10.1172/jci187372","DOIUrl":"https://doi.org/10.1172/jci187372","url":null,"abstract":"Group 3 innate lymphoid cells (ILC3s) have emerged as an important player in the pathogenesis of neutrophilic asthma. However, the regulatory mechanism supporting ILC3 responses in lung remains largely unclear. Here, we demonstrated that stem cell factor (SCF) expression is significantly increased and positively correlated with IL-17A and MPO expression in asthmatic patients. Notably, we identified ILC3 as a major IL-17A-producing responder to SCF in lung. In mice, SCF synergized with IL-1β/IL-23 to enhance pulmonary ILC3 activation and neutrophilic inflammation. Mechanistically, SCF promoted ILC3 proliferation and cytokine production. Transcriptomic analysis revealed that SCF treatment upregulated the genes related to proliferation and Th17 differentiation, associated with increased AKT and STAT3 signaling. In contrast, deficiency of SCF receptor, c-Kit, reduced ILC3 proliferation and IL-17A production, resulting in the amelioration of airway hyperreactivity (AHR) and neutrophilic inflammation in mouse neutrophilic asthma model. Furthermore, genetic deletion of SCF in fibroblasts revealed fibroblasts as the primary source of SCF for ILC3 activation in lung. Moreover, administration of imatinib, a c-Kit inhibitor, alleviated LPS, air pollution or ovalbumin/LPS-induced AHR and neutrophilic inflammation. Our findings elucidated a positive modulatory role of SCF/c-Kit signaling in ILC3 responses during neutrophilic inflammation, offering a potential therapeutic target for neutrophilic asthma.","PeriodicalId":520097,"journal":{"name":"The Journal of Clinical Investigation","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144652503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endocochlear potential contributes to hair cell death in TMPRSS3 hearing loss.","authors":"A Eliot Shearer,Yuan-Siao Chen,Stephanie L Rouse,Xiaohan Wang,Janmaris Marin Fermin,Kevin Ta Booth,Jasmine Moawad,Nicole Bianca Libiran,Jinan Li,Hae-Young Kim,Michael Hoa,Rafal Olszewski,Jing-Yu Lei,Ernesto Cabrera,Douglas J Totten,Bo Zhao,Jeffrey R Holt,Rick F Nelson","doi":"10.1172/jci186395","DOIUrl":"https://doi.org/10.1172/jci186395","url":null,"abstract":"Pathogenic variants in the gene TMPRSS3 are a common cause of hearing loss in humans, although the causal mechanisms remain unknown. Previous work has shown that Tmprss3Y260X/Y260X mice exhibit normal hair cell development, mechanosensory transduction, and spiral ganglion patterning, but experience rapid hair cell death from P12 to P14 at the onset of hearing. Here, we demonstrate that Tmprss3Y260X/Y260X mice display an early and temporary spike in endocochlear potential (EP) prior to the onset of hair cell death. In vitro experiments with cochlear explants from Tmprss3Y260X/Y260X mice and in vivo studies with Tmprss3Y260X/Y260X mice crossed with two different mutant models that lacked EP generation promoted hair cell survival. Furthermore, systemic administration of furosemide, a drug that reduces EP in vivo, reduced hair cell death in Tmprss3Y260X/Y260X mice. These findings suggest that extracellular factors, including EP, play a role in TMPRSS3-related hair cell survival and hearing loss, and suggest that modulating EP could be a therapeutic strategy.","PeriodicalId":520097,"journal":{"name":"The Journal of Clinical Investigation","volume":"29 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144652504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chemokine gradients spare graft endothelium from CD8+ T cell-mediated injury during allograft rejection.","authors":"Scott M Krummey,Jonathan S Bromberg","doi":"10.1172/jci193454","DOIUrl":"https://doi.org/10.1172/jci193454","url":null,"abstract":"T cell-mediated rejection (TCMR) develops after alloantigen-primed T cells migrate into an allograft to cause tissue damage. In contrast to antibody-mediated rejection, which creates lesions in the graft vasculature, injury to the graft vasculature is often limited during TCMR. In this issue of the JCI, Barba et al. investigated the mechanism by which the endothelium is spared from harm caused by graft-infiltrating CD8+ T cells. Endothelial cell protection was due to cell-extrinsic chemokine variations in the environment, rather than cell-intrinsic differences between endothelial and interstitial cells. The CXCL12 gradient in particular facilitated CD8+ T cell movement through the endothelial layer into the graft parenchyma. These findings suggest that targeting the CXCL12 pathway may prevent or alleviate TCMR.","PeriodicalId":520097,"journal":{"name":"The Journal of Clinical Investigation","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144629985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sensory neuron-expressed FGF13 controls nociceptive signaling in diabetic neuropathy models.","authors":"Aditya K Singh,Matteo Bernabucci,Nolan M Dvorak,Zahra Haghighijoo,Jessica Di Re,Nana A Goode,Feni K Kadakia,Laura A Maile,Olumarotimi O Folorunso,Paul A Wadsworth,Cynthia M Tapia,Pingyuan Wang,Jigong Wang,Haiying Chen,Yu Xue,Jully Singh,Kali Hankerd,Isaac J Gamez,Makenna Kager,Vincent Truong,Patrick Walsh,Stephanie I Shiers,Nishka Kuttanna,Hanyue Liao,Margherita Marchi,Erika Salvi,Ilaria D'Amato,Daniela D'Amico,Parsa Arman,Catharina G Faber,Rayaz A Malik,Marina de Tommaso,Dan Ziegler,Krishna Rajarathnam,Thomas A Green,Peter M Grace,Matthew R Sapio,Michael J Iadarola,Gregory D Cuny,Diana S Chow,Giuseppe Lauria Pinter,Steve Davidson,Dustin P Green,Jun-Ho La,Jin Mo Chung,Jia Zhou,Theodore J Price,Elizabeth Salisbury,Subo Yuan,Fernanda Laezza","doi":"10.1172/jci183749","DOIUrl":"https://doi.org/10.1172/jci183749","url":null,"abstract":"Nociception involves complex signaling, yet intrinsic mechanisms bidirectionally regulating this process remain unexplored. Here, we show that the fibroblast growth factor 13 (FGF13)/Nav1.7 protein-protein interaction (PPI) complex bidirectionally modulates nociception, and that the FGF13/Nav1.7 ratio is upregulated in type 2 diabetic neuropathy (T2DN). PW164, an FGF13/Nav1.7 channel C-terminal tail domain (CTD) PPI interface inhibitor, which reduces complex assembly, selectively suppressed Na+ currents sensitized by capsaicin-induced activation of TRPV1 channels in human induced pluripotent stem cell-derived (hIPSC-derived) sensory neurons and inhibited mechanical and thermal hyperalgesia in mice. FGF13 silencing mimics PW164 activity in culture and in vivo. Conversely, ZL192, an FGF13 ligand that stabilizes FGF13/Nav1.7 CTD assembly, sensitized Na+ currents in hIPSC-derived sensory neurons and exerted pronociceptive behavioral responses in mice. ZL192's effects were abrogated by FGF13 silencing in culture and in vivo and recapitulated by FGF13 overexpression. In a model of T2DN, PW164 injection reduced mechanical hyperalgesia locally and contralaterally without systemic side effects. In donor-derived dorsal root ganglia neurons, FGF13 and Nav1.7 proteins colocalized, and the FGF13/Nav1.7 protein ratio was upregulated in patients with T2DN. Lastly, we found that SCN9A variant V1831F, associated with painless diabetic neuropathy, abolished PW164-directed modulation of the FGF13/Nav1.7 PPI interface. Thus, FGF13 is a rheostat of nociception and promising therapeutic target for diabetic neuropathy pain.","PeriodicalId":520097,"journal":{"name":"The Journal of Clinical Investigation","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144630037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of a therapeutic humanized FSH-blocking antibody in obesity and Alzheimer's disease models.","authors":"Anusha R Pallapati,Funda Korkmaz,Satish Rojekar,Steven Sims,Anurag Misra,Judit Gimenez-Roig,Aishwarya Gangadhar,Victoria Laurencin,Anissa Gumerova,Uliana Cheliadinova,Farhath Sultana,Darya Vasilyeva,Liam Cullen,Jonathan Schuermann,Jazz Munitz,Hasni Kannangara,Surabhi Parte,Georgii Pevnev,Guzel Burganova,Zehra Tumoglu,Ronit Witztum,Soleil Wizman,Natan Kramskiy,Liah Igel,Fazilet Sen,Anna Ranzenigo,Anne Macdonald,Susan Hutchison,Abraham Jp Teunissen,Heather Burkart,Mansi Saxena,Yelena Ginzburg,Ki Goosens,Weibin Zhou,Vitaly Ryu,Ofer Moldavski,Orly Barak,Michael Pazianas,John Caminis,Shalender Bhasin,Richard Fitzgerald,Se-Min Kim,Matthew Quinn,Shozeb Haider,Susan Appt,Tal Frolinger,Clifford J Rosen,Daria Lizneva,Yogesh K Gupta,Tony Yuen,Mone Zaidi","doi":"10.1172/jci182702","DOIUrl":"https://doi.org/10.1172/jci182702","url":null,"abstract":"There is growing evidence for direct actions of follicle-stimulating hormone (FSH) on tissues other than the ovaries and testes. Blocking FSH action, either genetically or pharmacologically, protects against bone loss, fat gain, and memory loss in mice. We thus developed a humanized FSH-blocking antibody--MS-Hu6--as a lead therapeutic for three diseases of public health magnitude--osteoporosis, obesity and Alzheimer's disease (AD) that track together in post-menopausal women. Here, we report the crystal structure of MS-Hu6 and its interaction with FSH in atomistic detail. Using our Good-Laboratory-Practice-Compliant platform (21CFR58), we formulated MS-Hu6 and the murine equivalent Hf2 at an ultra-high concentration; both formulated antibodies displayed enhanced thermal and colloidal stability. A single injection of 89Zr-labelled MS-Hu6 revealed a beta-phase t½ of 89 and 131 hours for female and male mice, respectively, with retention in regions of interest. Female mice injected subcutaneously with Hf2 displayed a dose-dependent reduction in body weight and body fat. Hf2 also rescued recognition memory and spatial learning loss in a context- and time-dependent manner in AD-prone 3xTg and APP/PS1 mice. MS-Hu6 injected into African green monkeys (8 mg/kg) intravenously, and then subcutaneously at monthly intervals, was safe, and without effects on vitals, blood chemistries or blood counts. There was a notable ~4% weight loss in all four monkeys after the first injection, which continued in two of four monkeys. We thus provide IND-enabling data towards an upcoming first-in-human study.","PeriodicalId":520097,"journal":{"name":"The Journal of Clinical Investigation","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144639845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pancreatic ductal adenocarcinoma: the Everest of cancer biology.","authors":"Minh T Than,Ben Z Stanger","doi":"10.1172/jci191936","DOIUrl":"https://doi.org/10.1172/jci191936","url":null,"abstract":"","PeriodicalId":520097,"journal":{"name":"The Journal of Clinical Investigation","volume":"29 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144629976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}