Signal Transduction and Targeted Therapy最新文献

{"title":"Safety and immunogenicity of an HIV vaccine trial with DNA prime and replicating vaccinia boost.","authors":"Ying Liu,Wei Lv,Pu Shan,Dan Li,Ying-Qi Wu,You-Chun Wang,Yuan-Yuan Li,Qiang Liu,Jian-Sheng Wang,Yan-Ling Hao,Yong Liu,Wei-Jin Huang,Li Ren,Shu-Hui Wang,Tai-Sheng Li,Jing Xu,Yi-Ming Shao","doi":"10.1038/s41392-025-02259-y","DOIUrl":"https://doi.org/10.1038/s41392-025-02259-y","url":null,"abstract":"Developing a safe and effective vaccine remains a global priority for ending the human immunodeficiency virus (HIV) pandemic. All HIV vaccine trials with protein, DNA, non-replication vector or their combinations failed in the past. We constructed the HIV-1 CN54 env, gag, and pol genes into both DNA and replicating vaccinia virus Tiantan vectors. In phase Ia, 12 healthy adults were given high (n = 6) or low (n = 6) doses of recombinant vaccinia virus Tiantan vaccine (rTV), to test its safety dose. In phase Ib, 36 healthy adults were assigned to the DNA (n = 6), DNA-L/rTV (n = 12), DNA-H/rTV (n = 12), and placebo (n = 6) groups. The DNA vaccine was injected intramuscularly at weeks 0, 4, and 8 and rTV with a bifurcated needle at week 12. All vaccines tested were safe and well-tolerated; most of the adverse events (AEs) were mild to moderate. The most commonly observed AEs were redness and papule at rTV vaccination sites and axillary enlarged lymph nodes at the same rTV vaccination arm. Smaller cutaneous lesions and shorter healing time were observed in smallpox vaccine experienced subjects. The DNA prime-rTV boost regimen induced anti-gp120 IgG and polyfunctional CD4+ T cells. No significant differences of anti-HIV IgG and T cell responses were found between the two prime-boost groups with high and low DNA doses. Moreover, smallpox vaccine naïve subjects elicited higher T cell responses and anti-gp120 antibodies. The result of this trial supports further development of HIV vaccine with DNA and replicating vaccinia vector for advanced clinical trials.","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":"27 1","pages":"208"},"PeriodicalIF":39.3,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144533398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Signaling pathways and targeted therapy for pulmonary hypertension","authors":"Joseph Adu-Amankwaah, Yue Shi, Hequn Song, Yixuan Ma, Jia Liu, Hao Wang, Jinxiang Yuan, Kun Sun, Qinghua Hu, Rubin Tan","doi":"10.1038/s41392-025-02287-8","DOIUrl":"https://doi.org/10.1038/s41392-025-02287-8","url":null,"abstract":"<p>Pulmonary hypertension (PH) is a global health issue characterized by high mortality. The main targets for current therapies in PH focus on the prostacyclin, nitric oxide, and endothelin pathways. While the approaches targeting these pathways form the foundation of standard PH treatment, the challenge remains to develop more effective therapeutic strategies. Evidence of pathological characteristics in PH illustrates other cell signaling pathways that also participate in the proliferation, apoptosis, extracellular matrix remodeling, mitochondrial dysfunction, inflammation, endothelial-to-mesenchymal transition, ferroptosis, pyroptosis, and the intricate network of cell-cell interactions of endothelial cells, smooth muscle cells, fibroblasts, and macrophages. In this review, we explore the roles of twenty key signaling pathways in PH pathogenesis. Furthermore, the crosstalks among some pathways offer a more detailed understanding of the complex mechanisms of PH. Considering the crucial role of signaling pathways in PH progression, targeting these aberrant signaling or their hub molecules offers great potential for mitigating PH pathology. This review delves into a variety of therapeutic approaches for PH that target critical signaling pathways and network interactions, including gene therapy, cell therapy, and pharmacological interventions. Supported by evidence from both animal studies and clinical trials, these strategies aim to reverse pathological alterations in pulmonary vessels and restore their normal function, addressing the significant health challenges associated with PH.</p>","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":"51 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144520881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modification of lysine residues in proteins: a novel posttranslational effect of vitamin C","authors":"Dieter Kabelitz","doi":"10.1038/s41392-025-02288-7","DOIUrl":"https://doi.org/10.1038/s41392-025-02288-7","url":null,"abstract":"<p>In a recent article published in <i>Cell</i>, He and colleagues reported that vitamin C (VitC) modifies lysine residues in proteins and peptides, thereby forming vitcyl-lysine, a process they have called vitcylation. They show that vitcylation of signal transducer and activator of transcription-1 (STAT1) increases its phosphorylation and thereby promotes interferon pathway activation in cancer cells and anti-tumor immunity.¹</p>","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":"1 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144515538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serine/threonine/tyrosine kinase 1 drives pancreatic carcinogenesis via GSK3β sequestration-mediated Wnt/β-catenin pathway hyperactivation","authors":"Cefan Zhou, Xueying Dong, Shi Li, Yue Xi, Yuan Liu, Xuehong Qian, Ziyan Song, Li Zhou, Rui Zhang, Hao Lyu, Shuai Xiao, Dong Guo, Qi Zhang, Weiyong Liu, Yan Xiong, Zhentian Wang, Chaojun Yan, Zijian Zhang, Haichuan Zhu, Xing-Zhen Chen, Zhiyin Song, Jingfeng Tang","doi":"10.1038/s41392-025-02292-x","DOIUrl":"https://doi.org/10.1038/s41392-025-02292-x","url":null,"abstract":"<p>The Wnt/β-catenin pathway is strongly relevant to pancreatic cancer progression, poor prognostic outcomes, and elevated cancer-related mortality. However, the mechanism underlying continuously activated Wnt/β-catenin signaling in pancreatic cancer, a context in which adenomatous polyposis coli (APC) mutations are rarely observed, remains poorly understood. In this study, we investigated the role of STYK1 in regulating canonical Wnt/β-catenin signaling and pancreatic cancer tumorigenesis using the <i>LSL-Kras</i>^<i>G12D</i>; <i>Trp53</i>^{<i>R172H/+</i>}; <i>Pdx1</i>^<i>Cre</i> mouse model. Our findings demonstrate that STYK1 directly binds to β-catenin and GSK3β, inhibiting GSK3β activity by increasing the level of its kinase-inactive form, which is phosphorylated at S9, and promoting its sequestration into MVBs. We further showed that STYK1-mediated GSK3β sequestration is impaired by autophagy inhibitors or in ATG7 knockout cells, linking this process to autophagic regulation. Structural analysis identified conserved tyrosine-based (Y191QRL194) and dileucine-based (GDLL203-204) sorting motifs in STYK1, which facilitate clathrin/AP2-dependent internalization essential for GSK3β sequestration. The phosphorylation of STYK1 at Y191 by BLK kinase enhances its interaction with AP2, thereby accelerating GSK3β sequestration and subsequent Wnt/β-catenin pathway activation. Notably, inhibitory peptides targeting either the STYK1-β-catenin or the STYK1-GSK3β interface significantly suppressed pancreatic cancer development in vitro and in vivo, underscoring their therapeutic potential. Collectively, these results elucidate a novel STYK1-driven mechanism for Wnt/β-catenin activation in APC-independent pancreatic cancer and provide preclinical evidence for targeting STYK1-mediated signaling as a therapeutic strategy.</p>","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":"9 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144515542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tailoring a novel colorectal cancer stem cell-targeted therapy by inhibiting the SMYD3/c-MYC axis","authors":"Martina Lepore Signorile, Elisabetta Di Nicola, Giovanna Forte, Paola Sanese, Candida Fasano, Vittoria Disciglio, Katia De Marco, Marialaura Latrofa, Loris De Cecco, Marica Ficorilli, Marta Lucchetta, Erica Torchia, Chiara Dossena, Giusy Bianco, Vito Spilotro, Claudia Ferroni, Nicoletta Labarile, Raffaele Armentano, Francesco Albano, Anna Mestice, Gianluigi Gigante, Valerio Lantone, Giuliano Lantone, Leonardo Vincenti, Alberto Del Rio, Greta Varchi, Valentina Grossi, Cristiano Simone","doi":"10.1038/s41392-025-02290-z","DOIUrl":"https://doi.org/10.1038/s41392-025-02290-z","url":null,"abstract":"<p>Cancer stem cells (CSCs) are responsible for colorectal cancer (CRC) chemoresistance, recurrence, and metastasis. Therefore, identifying molecular stemness targets that are involved in tumor growth is crucial for effective treatment. Here, we performed an extensive in vitro and in vivo molecular and functional characterization, revealing the pivotal role of the lysine methyltransferase SET and MYND Domain Containing 3 (SMYD3) in colorectal cancer stem cell (CRC-SC) biology. Specifically, we showed that SMYD3 interacts with and methylates c-MYC at K158 and K163, thereby modulating its transcriptional activity, which is implicated in stemness and colorectal malignancy. Our in vitro data suggest that SMYD3 pharmacological inhibition or its stable genetic ablation affects the clonogenic and self-renewal potential of patient-derived CRC-SCs and organoids by altering their molecular signature. Moreover, we found that SMYD3 stable knock-out or pharmacological inhibition drastically reduces CRC tumorigenicity in vivo and CRC-SC metastatic potential. Overall, our findings identify SMYD3 as a promising therapeutic target acting directly on c-MYC, with potential implications for countering CRC-SC proliferation and metastatic dissemination.</p>","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":"46 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144515546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The mechanosensitive adhesion G protein-coupled receptor 133 (GPR133/ADGRD1) enhances bone formation","authors":"Juliane Lehmann, Hui Lin, Zihao Zhang, Maren Wiermann, Albert M. Ricken, Franziska Brinkmann, Jana Brendler, Christian Ullmann, Luisa Bayer, Sandra Berndt, Anja Penk, Nadine Winkler, Franz Wolfgang Hirsch, Thomas Fuhs, Josef Käs, Peng Xiao, Torsten Schöneberg, Martina Rauner, Jin-Peng Sun, Ines Liebscher","doi":"10.1038/s41392-025-02291-y","DOIUrl":"https://doi.org/10.1038/s41392-025-02291-y","url":null,"abstract":"<p>Osteoporosis represents an increasing health and socioeconomic burden on aging societies. Current therapeutic options often come with potentially severe side effects or lack long-term efficacy, highlighting the urgent need for more effective treatments. Identifying novel drug targets requires a thorough understanding of their physiological roles. Genome-wide association studies in humans have linked gene variants of the adhesion G protein-coupled receptor 133 (GPR133/ADGRD1) to variations in bone mineral density and body height. In this study, we explore the impact of GPR133/ADGRD1 on osteoblast differentiation and function. Constitutive and osteoblast-specific knockouts of <i>Gpr133/Adgrd1</i> in mice lead to reduced cortical bone mass and trabecularization in the femurs and vertebrae — features characteristic of osteoporosis. This osteopenic phenotype in receptor-deficient mice is caused by impaired osteoblast function, which, in turn, promotes increased osteoclast activity. At the molecular level, GPR133/ADGRD1 regulates osteoblast function and differentiation through a combined activation mechanism involving interaction with its endogenous ligand, protein tyrosine kinase 7 (PTK7), and mechanical forces. This is demonstrated in vitro through stretch assays and in vivo via a mechanical loading experiment. Further in vitro analysis shows that GPR133/ADGRD1-mediated osteoblast differentiation is driven by cAMP-dependent activation of the β-catenin signaling pathway. Activation of GPR133/ADGRD1 with the receptor-specific ligand AP-970/43482503 (AP503) enhances osteoblast function and differentiation, both in vitro and in vivo, significantly alleviating osteoporosis in a mouse ovariectomy model. These findings position GPR133/ADGRD1 as a promising therapeutic target for osteoporosis and other diseases characterized by reduced bone mass.</p>","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":"26 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144515541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reshaping the tumor microenvironment of cold soft-tissue sarcomas with anti-angiogenics: a phase 2 trial of regorafenib combined with avelumab","authors":"Maud Toulmonde, Jean-Philippe Guégan, Mariella Spalato-Ceruso, Thibaud Valentin, Rastilav Bahleda, Florent Peyraud, Christophe Rey, Michèle Kind, Coralie Cantarel, Carine Bellera, Lucile Vanhersecke, Alban Bessede, Antoine Italiano","doi":"10.1038/s41392-025-02278-9","DOIUrl":"https://doi.org/10.1038/s41392-025-02278-9","url":null,"abstract":"<p>The majority of sarcomas are under the influence of a tumor microenvironment that dampens immune activity, resulting in resistance to monoclonal antibodies targeting immune checkpoints and reduced clinical effectiveness. Preclinical studies indicate that targeting abnormal neoangiogenesis by inhibiting vascular endothelial growth factor receptor (VEGFR) can alter the TME, thereby promoting T cell infiltration and increasing tumor immunogenicity. The REGOMUNE study, a phase II clinical trial, assessed the therapeutic combination of regorafenib, a multityrosine kinase inhibitor that targets VEGFR2 and the PD-L1 blocker avelumab, in individuals with advanced “cold” STS characterized by a lack of mature tertiary lymphoid structures (mTLS). Forty-nine mTLS-negative STS patients were enrolled, including leiomyosarcoma (45%), synovial sarcoma (18%), and other subtypes. The objective response rate was 11.0% (95% CI: 4.0% - 22.0%), with median progression-free survival and overall survival of 1.8 months (95% CI, 1.7–3.5 months) and 15.1 months, respectively. Frequent adverse events included grade 1 or 2 palmar-plantar erythrodysesthesia, fatigue, and diarrhea. On-treatment multiplex immunofluorescence analysis revealed significant increases in CD8 + T cell and B cell infiltration and PD1 expression on immune cells. Plasma analysis indicated significant upregulation of soluble PD-L1 (sPD-L1) levels and tryptophan consumption. Overall, these results indicate that anti-angiogenic therapy modulates the tumor microenvironment in patients with cold STS and highlight the need for complementary strategies to enhance the functional activity of immune cells in this particular setting. Clinical trial registration number: NCT03475953</p>","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":"57 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144500577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From obscurity to opportunity: targeting Neuregulin 1 fusions in solid tumors","authors":"Sofía Llorente, Angela Lamarca, Tian V. Tian","doi":"10.1038/s41392-025-02283-y","DOIUrl":"https://doi.org/10.1038/s41392-025-02283-y","url":null,"abstract":"","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":"630 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144500571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"D-lactate and glycerol as potential biomarkers of sorafenib activity in hepatocellular carcinoma","authors":"Silvia Pedretti, Francesca Palermo, Miriana Braghin, Gabriele Imperato, Pasquale Tomaiuolo, Meral Celikag, Marta Boccazzi, Veronica Vallelonga, Lorenzo Da Dalt, Giuseppe Danilo Norata, Giorgia Marisi, Ilario Giovanni Rapposelli, Andrea Casadei-Gardini, Serena Ghisletti, Maurizio Crestani, Emma De Fabiani, Nico Mitro","doi":"10.1038/s41392-025-02282-z","DOIUrl":"https://doi.org/10.1038/s41392-025-02282-z","url":null,"abstract":"<p>Sorafenib, a multi-kinase inhibitor for advanced hepatocellular carcinoma (HCC), often encounters resistance within months of treatment, limiting its long-term efficacy. Despite extensive efforts, reliable plasma biomarkers to monitor drug activity remain elusive. Here, we demonstrate that metabolic reprogramming is a strategic response implemented by cancer cells to survive the therapeutic pressure. Sorafenib suppresses oxidative phosphorylation by disrupting electron transport chain supercomplex assembly and enhancing glycolysis. To mitigate the accumulation of harmful glycolytic byproducts such as advanced glycation end-products (AGEs), sorafenib-treated cells reroute excess dihydroxyacetone phosphate (DHAP) toward glycerol-3-phosphate (G3P) synthesis, supporting glycerolipid metabolism, NAD⁺ regeneration, and redox balance, rather than producing D-lactate via the glyoxalase pathway. Alongside, resistant cells enhance serine metabolism to boost glutathione synthesis, reinforcing antioxidant defenses. Additionally, sorafenib increases reliance on exogenous non-esterified free fatty acids and triglycerides for phospholipid remodeling. The combined effects of glycerolipid remodeling and enhanced antioxidant capacity facilitate ferroptosis escape, diminishing sorafenib’s activity. Leveraging these metabolic insights, we validate our findings by investigating plasma metabolites alteration in HCC patients. We identify D-lactate accumulation as a predictor of treatment response and glycerol accumulation as a marker of resistance, highlighting their potential as novel biomarkers for sorafenib activity. As sorafenib is used in advanced HCC, early detection of treatment response is critical to guiding the therapeutic decision, optimizing treatment strategies, and improving patient outcomes.</p>","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":"64 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144500576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multicenter phase 1/2 study of onatasertib, a dual TORC1/2 inhibitor, combined with the PD-1 antibody toripalimab in advanced solid tumors.","authors":"Pei Shu,Xiaoyu Li,Qi Zhou,Guiling Li,Keqiang Zhang,Li Yuan,Yixian Liu,Qiu Li,Yongsheng Wang,Hui Xie,Li Zheng","doi":"10.1038/s41392-025-02281-0","DOIUrl":"https://doi.org/10.1038/s41392-025-02281-0","url":null,"abstract":"Preclinical studies have indicated that the combination of mTORC1/2 inhibitors with PD-1 antibodies exhibits synergistic effects on solid tumors. However, no clinical data supporting this combination have been reported. Therefore, we conducted a clinical trial (NCT04337463) to investigate the efficacy and safety of combining onatasertib, an mTORC1/2 inhibitor, with toripalimab, a PD-1 antibody in patients with advanced solid tumors. This open-label, phase 1/2 clinical trial included dose escalation and dose expansion cohorts to evaluate safety, tolerability, objective response rate (ORR), disease control rate (DCR) and progression-free survival (PFS). A total of 46 patients were enrolled and received onatasertib at doses of 15 mg, 20 mg, or 30 mg once daily (QD), combined with toripalimab 240 mg every 3 weeks (Q3W). No dose-limiting toxicities were observed, and the most common grade 3 or 4 treatment emergent adverse events were lymphopenia (23.9%) and rash (19.6%). The overall ORR was 26.1%, with a DCR of 73.9%, and a median PFS of 4.3 months. In cervical cancer patients, regardless of PD-L1 expression, the ORR was 52.4%, DCR was 90.5% and median PFS was 5.8 months. Notably, the 15 mg combination dose demonstrated a median PFS of 7.8 months. In conclusion, the safety profile of onatasertib in combination with toripalimab was manageable and showed encouraging clinical activity in advanced solid tumors, particularly among cervical cancer patients, irrespective of PD-L1 expression. The recommended phase 2 dose for the combination was determined to be onatasertib 15 mg QD and toripalimab 240 mg Q3W.","PeriodicalId":21766,"journal":{"name":"Signal Transduction and Targeted Therapy","volume":"21 1","pages":"198"},"PeriodicalIF":39.3,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144478709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}