Undisclosed YAP/TAZ-TEAD inhibitor / Hanmi - LARVOL DELTA

Pipeline to evaluate YAP-TEAD inhibitors indicates TEAD inhibition represses NF2-mutant mesothelioma. (PubMed, Life Sci Alliance) - "Here, we develop a high-content pipeline that enables a comparative analysis of currently developed YAP/TAZ-TEAD inhibitors...We identify genetic compensation of the Hippo pathway transcriptional module, with implications for therapeutic targeting, and implement Cell Painting to develop a detailed morphological profiling pipeline that enables further characterisation, quantification, and analysis of off-target effects. Our pipeline is scalable and allows us to establish specificity and comparative potency within cancer-relevant assays in a clinically relevant cellular model of pleural mesothelioma."

Journal • Malignant Pleural Mesothelioma • Mesothelioma • Oncology • Pleural Mesothelioma • Solid Tumor • NF2

Hyper-responsiveness of cancer stem cells to microenvironmental cues controls metastasis and therapy response through YAP/TAZ/TEAD. (PubMed, bioRxiv) - "Targeting inputs to the YAP/TAZ/TEAD node reversed chemotherapy-induced enrichment of CSCs in lung metastases. Different population dynamics for breast cancer stem cells (CSCs) and their differentiated progeny in early metastatic colonizationCSCs are hyper-responsive to microenvironmental cues and serve as sensors of local conditions for the tumorMany microenvironmental inputs converge on YAP/TAZ to regulate self-renewal vs differentiation fate decisions in the CSCTargeting YAP/TAZ input pathways blocks chemotherapy-induced enrichment of CSCs."

Journal • Breast Cancer • Oncology • Solid Tumor

miR-127-5p-Enriched Extracellular Vesicles Modulate the Hippo Pathway to Counteract Steroid-Induced Osteonecrosis pathology of the Femoral Head. (PubMed, Free Radic Biol Med) - "Quantitative real-time PCR revealed that miR-127-5p is significantly downregulated in SONFH-hBMSCs, leading to the upregulation of LATS2 and the suppression of YAP/TAZ-TEAD activity, which are crucial for osteogenesis...However, miR-127-5p-enriched EVs reversed these effects, restoring osteogenic differentiation, improving bone microarchitecture, and enhancing gait performance in SONFH models. These findings suggest that miR-127-5p downregulation plays a critical role in SONFH progression and that miR-127-5p-enriched EVs may offer a promising therapeutic strategy to treat SONFH by promoting bone regeneration and improving functional outcomes."

Journal • LATS2 • MIR127

Cytolethal Distending Toxin-increased DNA damage and ploidy involve the YAP/TAZ-TEAD signaling pathway. (PubMed, J Infect Dis) - "Overall, these data show that infection with genotoxin-producing bacteria involves the YAP/TAZ-TEAD signaling pathway to control ploidy following DNA damage in epithelial cells."

Journal • Infectious Disease • Oncology

Atypical Hippo signaling network: uncovering novel insights into head and neck cancer biology and advancements in precision intervention. (PubMed, Front Cell Dev Biol) - "Current therapeutic innovation focuses on molecular diagnostics and precision targeting approaches, including direct YAP/TAZ-TEAD complex inhibitors, upstream receptor modulators, and rational combinations with immune checkpoint blockade. Future investigations should employ multi-omics profiling to delineate tumor subtype-specific regulatory architectures while advancing novel drug delivery platforms. These efforts promise to translate mechanistic insights into multi-targeted therapeutic strategies capable of overcoming resistance mechanisms and improving survival outcomes for this therapeutically challenging malignancy."

Journal • Review • Head and Neck Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • ER • NDRG1

TEADlight, a bright dynamic reporter for live detection of YAP/TAZ-TEAD signaling. (PubMed, Dev Biol) - "Moreover, TEADlight revealed dynamic responses in somites in vivo, and to contact inhibition and spatial constraints in vitro. Therefore, TEADlight enables real-time, high-sensitivity analysis of YAP/TAZ-TEAD signaling across developmental and cellular models, opening new avenues for studying the activity of this pathway in physiological and pathological processes."

Journal

Hippo pathway effectors are associated with glioma patient survival, control cell proliferation and sterol metabolism through TEAD3. (PubMed, Brain Pathol) - "Pharmacological inhibition of YAP/TAZ-TEAD interaction by Verteporfin significantly decreased tumor cell growth, whereas specific inhibition of TEAD3 did not impact cell proliferation but affected sterol/cholesterol biosynthetic and metabolic processes. This study contributes to a better understanding of the role of Hippo effectors in glioblastoma pathophysiology. These transcription factors, particularly TEAD3, could potentially serve as therapeutic targets, especially considering recent data on cholesterol homeostasis in glioblastomas."

Journal • Brain Cancer • Glioblastoma • Glioma • Oncology • Solid Tumor • TEAD3

Transcription Factors and Coregulators in Schwann Cell Differentiation, Myelination, and Remyelination: Implications for Peripheral Neuropathy. (PubMed, J Neurosci Res) - "Processes of differentiation, myelination, and remyelination of SCs are tightly modulated by a complex network of transcription factors and coregulators, including Sox10, Oct6/Pou3f1, Krox20/Egr2, Nab1/2, YY1, COUP-TFII/NR2F2, YAP/TAZ-TEAD1, c-Jun, Sox2, Zeb2, and Etv1/Er81...Thus, this review briefly introduces processes of differentiation, myelination, and remyelination of SCs and explores the role and molecular mechanisms of each transcription factor and coregulator in differentiation and myelination of SCs and their remyelination following nerve injury. Clinical implications for peripheral neuropathies associated with specific gene mutations and variations of transcription factors and coregulators affecting SC biology are also discussed."

Journal • Review • Genetic Disorders • Pain • ETV1 • JUN • SOX10 • SOX2 • TEAD1 • YY1 • ZEB2

The cardiac glycoside periplocymarin sensitizes gastric cancer to ferroptosis via the ATP1A1-Src-YAP/TAZ-TFRC axis. (PubMed, Phytomedicine) - "Our findings establish the cardiac glycoside PPM as a novel ferroptosis sensitizer that targets ATP1A1 to activate the Src-YAP/TAZ-TFRC axis, providing mechanistic insights for repurposing cardiac glycosides as ferroptosis modulators in precision combinatorial cancer therapy."

Journal • Cardiovascular • Gastric Cancer • Oncology • Solid Tumor • ATP1A1

TEAD inhibition as a therapeutic strategy for diffuse-type gastric cancer (AACR 2025) - "Therefore, we evaluated the activity and mechanism of TEAD inhibitors in DGC preclinical models. Gastric cancer patient-derived organoids (PDOs) and cell lines were treated with TEAD inhibitors (VT103, VT107) and/or 5-fluorouracil (5-FU) for in vitro assays evaluating cell proliferation or invasion. The YAP/TAZ-TEAD pathway is an important driver of gastric cancer growth and metastasis, particularly in DGC where it may promote EMT. TEAD inhibition reduces gastric cancer growth and invasion in vitro and in vivo in preclinical models and demonstrates synergistic activity with 5-FU chemotherapy. These results suggest a potential role for further investigation of clinical efficacy of TEAD inhibitors in patients with DGC."

Gastric Cancer • Oncology • Solid Tumor • CASP3 • CDH1 • KRAS • SNAI2 • TEAD1 • TP53 • YAP1

Moxidectin unravels the role of Hippo-YAP pathway in maintaining immunity of glioblastoma multiforme. (PubMed, Mol Cancer Ther) - "Inhibition of MEK-ERK by moxidectin ultimately led to blockade of the nuclear translocation and transcriptional activity of YAP/TAZ-TEAD complex in various GBM cells. Chronic moxidectin treatment did not cause any toxicity in mice based on our toxicological evaluation. Moxidectin is an FDA approved drug, findings from our study will promote its clinical investigation as a potential therapeutic agent for GBM patients."

Journal • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

High dose methylprednisolone mediates YAP/TAZ-TEAD in vocal fold fibroblasts with macrophages. (PubMed, Sci Rep) - "The pro-fibrotic effects of glucocorticoids may lead to a suboptimal therapeutic response for vocal fold (VF) pathology. Verteporfin attenuated upregulation of CCN2, but not PTGS2 downregulation. High concentration methylprednisolone induced nuclear localization of S211-pGR and upregulated fibrotic genes mediated by YAP/TAZ activation."

Journal • Fibrosis • Immunology • Inflammation • Otorhinolaryngology • ACTA2 • COL1A1 • CTGF • CXCL10 • PACERR • PTGS2

Liraglutide improves senescence and ameliorating diabetic sarcopenia via the YAP-TAZ pathway. (PubMed, J Diabetes Complications) - "High glucose promotes muscle cell aging and sarcopenia, processes that liraglutide can attenuate by modulating the YAP/TAZ signaling pathway. This study underscores liraglutide's potential to alleviate muscle degeneration in diabetic sarcopenia through its regulatory impact on critical aging pathways."

Journal • Diabetes • Metabolic Disorders • Sarcopenia • Type 2 Diabetes Mellitus • CCND1 • CDKN1A • TP53

Prognostic Stratification of Epithelioid Pleural Mesothelioma Based on the Hippo-TEADs Network. (PubMed, Cancers (Basel)) - "Higher levels of downstream Hippo effectors are associated with poor response to platinum-pemetrexed doublet and worse OS. The stratification of ePM based on the activation of the YAP/TAZ-TEAD axis is an intriguing approach in the light of the inhibitors of this signaling that are currently under investigation."

Journal • Epithelioid Pleural Mesothelioma • Malignant Pleural Mesothelioma • Mesothelioma • Oncology • Pleural Mesothelioma • Solid Tumor • VSIR • WWTR1 • YAP1

LATS1/2 inactivation in the mammary epithelium drives the evolution of a tumor-associated niche. (PubMed, EMBO Rep) - "We further show that inhibition of the YAP/TAZ-associated TEAD family of transcription factors blocks the development of the carcinomas and associated microenvironment. These observations demonstrate that carcinomas resulting from Hippo pathway dysregulation in the mammary epithelium are sufficient to drive cellular events that promote a basal-like tumor-associated niche and suggest that targeting dysregulated YAP/TAZ-TEAD activity may offer a therapeutic opportunity for basal-like mammary tumors."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • LATS1 • LATS2 • TGFB1

FAK mediates mechanical signaling to maintain epithelial homeostasis through YAP/TAZ-TEADs. (PubMed, Histochem Cell Biol) - "Finally, we used primary mouse epithelial cells to reconstruct the epithelium in vitro and found that FAK inhibition led to both a reduction in YAP/TAZ activity and an increase of differentiation in the basal layer cells. In conclusion, our findings reveal that FAK mediates mechanical signaling to maintain epithelial homeostasis via YAP/TAZ-TEADs."

Journal

The recent advances and implications in cancer therapy for the hippo pathway. (PubMed, Curr Opin Cell Biol) - "In this review, we discuss how the emerging role of biomolecular condensates regulates the activity of the pathway components, and how dysregulation of the pathway leads to cancer. Lastly, we highlight the therapeutic modalities which target YAP/TAZ-TEAD interaction for cancer therapy."

Journal • Review • Oncology

Distinct effects of Hippo-YAP/TAZ and YAP/TAZ-TEAD in epithelial maintenance and repair. (PubMed, Biochem Biophys Res Commun) - "These findings indicate that Hippo-mediated YAP/TAZ regulation may extend beyond TEAD-dependent transcription. Our work clarifies the distinct contributions of Hippo-YAP/TAZ signaling and YAP/TAZ-TEAD interaction to epithelial maintenance and provides a basis for the development of therapeutic strategies targeting YAP/TAZ in epithelial disorders."

Journal

Noncanonical role of Golgi-associated macrophage TAZ in chronic inflammation and tumorigenesis. (PubMed, Sci Adv) - "Thus, targeted therapies being developed against YAP/TAZ-TEAD are ineffective in macrophages. Together, our results introduce Golgi-associated TAZ as a potential molecular target for therapeutic intervention to treat tumor progression and chronic inflammatory diseases."

IO biomarker • Journal • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Oncology

miR-424-5p Promotes Proliferation, Migration and Invasion of Colorectal Cancer Cells via the Targeting TXNIP/Hippo Axi. (PubMed, Int J Gen Med) - "And disordered Hippo pathway and YAP/TAZ-TEAD activity are related to tumor progression...The study clarify a novel miR-424-5p/TXNIP/Hippo signaling pathway that facilitated CRC cells proliferation, migration and invasion. The above findings suggested that miR-424-5p and TXNIP might serve as the potential therapeutic targets for CRC patients."

Journal • Acute Kidney Injury • Colorectal Cancer • Gastric Cancer • Genito-urinary Cancer • Hepatology • Kidney Cancer • Liver Cancer • Lung Cancer • Nephrology • Oncology • Pancreatic Cancer • Renal Cell Carcinoma • Renal Disease • Solid Tumor • MIR424 • TXNIP

Targeting YAP/TAZ-TEAD signaling as a therapeutic approach in head and neck squamous cell carcinoma. (PubMed, Cancer Lett) - "Here, we provide the pre-clinical evidence for the antitumor activity of novel smTEADi, SW-682 in HPV-negative HNSCC. A HNSCC-specific TEADi target gene set was defined from RNA-seq data, which is highly expressed in HNSCC tissues and predicts poor prognosis of HPV-negative HNSCC patients. Our results underscore that YAP/TAZ-TEAD-mediated growth-promoting programs represent a vulnerability in HPV-negative HNSCC, thus providing a pre-clinical rationale for the future evaluation of YAP/TAZ-TEAD targeting strategies as a therapeutic approach for HPV-negative HNSCC patients."

Journal • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • FAT1 • WWTR1 • YAP1

Towards the design of ligands of the internal pocket TEADs C-terminal domain. (PubMed, Eur J Med Chem) - "Soaking with hTEAD2 gave seven new crystal structures where the ligands occupied palmitate pocket. 5-Benzyloxyindoles armed with vinylsulfamide moiety inhibit YAP/TAZ-TEAD target genes expression and breast cancer cell proliferation at micromolar concentration."

Journal • Breast Cancer • Oncology • Solid Tumor • TEAD2

YAP/TAZ Target Genes may Determine the Self-renewal and Survival of Glioblastoma Stem Cells (SNO 2024) - "Furthermore, our research has demonstrated that inhibiting YAP/TAZ activity with the drug Verteporfin induces apoptosis and promotes growth arrest in patient-derived EGFR-amplified/mutant glioblastoma models. Our findings highlight YAP/TAZ-TEAD as key mediators of glioblastoma stem cell (GSC) self-renewal and survival...Our research seeks to uncover the epigenetic basis of YAP/TAZ dependencies and to determine which genes and cellular processes are critical for tumor stem cell survival, tumor progression, and sensitivity to YAP/TAZ inhibition. These target genes could serve as biomarkers for predicting therapeutic response to YAP/TAZ inhibitors in glioblastoma."

Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • MYC • SOX2 • TAFAZZIN

Identification and Targeting of Tumor Driver Schwann(NF2loss) Cells in Sporadic and NF2-Related Vestibular Schwannomas (SNO 2024) - "We report that Schwann(NF2loss) cells are key tumor drivers in VS. These cells are highly proliferative (YAP/TAZ-TEAD axis), drive angiogenesis (VEGFA expression), and promote tumor mass accretion (macrophage influx via M-CSF/IL-34 pathway) that can all be targeted via TEAD inhibition."

Brain Cancer • Genetic Disorders • Neurofibromatosis • Oncology • Solid Tumor • CSF1 • EGFR • HIF1A • IL34 • NF2 • NRG1 • POSTN • TEAD1 • YAP1

Targeting of the YAP/TAZ-TEAD axis diminishes viability and differentiation potential in pediatric high-grade glioma (SNO 2024) - "Use of Verteporfin (VP), a FDA-approved YAP/TAZ small molecule inhibitor, mimicked the effects seen by YAP genetic depletion. Results from our work showing that YAP/TAZ-TEAD inhibition is a promising therapeutic avenue for management of pHGGs will be presented. Further pre-clinical work will follow to correlate observation and understand the therapeutic efficacy of YAP/TAZ-TEAD inhibition for pHGG treatment."

Clinical • Brain Cancer • CNS Tumor • Glioma • Malignant Glioma • Oncology • Pediatrics • Solid Tumor