AZD6482 / AstraZeneca, Wuhan University, ThromBio - LARVOL DELTA

A Rac-PI3Kβ feedback loop drives GPVI-dependent platelet activation. (PubMed, iScience) - "Inhibition of Rac/Cdc42 in wild-type platelets phenocopied the knockin defects, supporting a direct role for Rho GTPases in PI3Kβ activation. Conversely, Rac activation was impaired in RBD-mutant and AZD6482-treated platelets, revealing a Rac-PI3Kβ feedback loop that amplifies GPVI-dependent platelet activation."

Journal • Thrombosis • CDC42 • PIK3CB

VEGFC as a prognostic cytokine biomarker linking lymph node metastasis to immune suppression in breast cancer. (PubMed, Eur Cytokine Netw) - "VEGFC is a robust, independent precision biomarker specifically indicating poor prognosis in Luminal breast cancers. It is significantly associated with an immune-excluded TME, suggesting that targeting the VEGFC axis may offer a novel strategy to reverse immune evasion."

Biomarker • Journal • Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • BRCA • CD8 • VEGFC

A Rac–PI3Kβ Feedback Loop Drives GPVI-Dependent Platelet Activation (ISTH 2026) - "Functional studies were performed on human platelets in the presence of the Rac/CDC42 inhibitor EHT1864 and/or PI3Kβ inhibitor AZD6482...Reciprocal effects on Rac highlight a bidirectional feedback loop, which may also operate in human platelets. DOI*10.1016/j.rpth.2026.105263"

Thrombosis • PIK3CB • PLCG2 • PLEK • SYK

PI3Kß Mediates Immune Microenvironment Remodeling and Contributes to B7H3 Monoclonal Antibody Resistance in PTEN-Deficient Prostate Cancer (AUA 2026) - "The PI3Kβ inhibitor AZD6482 outperforms the PI3Kα inhibitor in PTEN-deficient PCa by enhancing the function of effector immune cells. Combining AZD6482 with B7H3 mAb improves therapeutic efficacy but induces the upregulation of PD-1+CD4+ T cells, suggesting that targeting the PD-1 pathway could be a potential strategy to overcome resistance. These findings support the development of combination strategies involving PI3Kβ inhibition and immune checkpoint targeting for the treatment of PTEN-deficient PCa."

IO biomarker • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CD276 • CD4 • CD8 • IFNG • PIK3CA • PIK3CB • PTEN • TNFA

Development and validation of a prognosis model for low-grade gliomas based on metabolic gene risk scoring and immune microenvironment interaction. (PubMed, Discov Oncol) - "This study constructed and validated a metabolism-driven prognostic model. The model enables prognostic stratification of LGG patients and links high-risk scores to metabolic dysregulation and an immunosuppressive microenvironment characterized by M2 macrophage enrichment, based on multi-omics data. Mechanistic exploration indicates this association is particularly pronounced in myeloid cells, predominantly within metabolism-related M2 macrophage subpopulations. Furthermore, computational analysis suggests differences in drug sensitivity between risk groups and identifies potential therapeutic compounds, providing clues for future exploration of therapeutic strategies targeting metabolic-immune interactions."

Journal • Tumor mutational burden • Brain Cancer • Glioma • Metabolic Disorders • Oncology • Solid Tumor • ACACB • ALOX15B • CYP17A1 • GLRX • GPX7 • IDH1 • TMB • TYMS

A Cuproptosis-Related lncRNA Signature Predicts Prognosis and Shapes the Immune Landscape in Primary Lower-Grade Glioma. (PubMed, Genet Res (Camb)) - "Several prospective drugs targeting samples with high scores were predicted, namely, MG-132, PLX-4720, AZD6482, and BMS-536924. Moreover, experiments conducted in vitro demonstrated that knockdown of the expression of the CRLs TPRG1-AS1 and LYRM4-AS1 might impair the migration and proliferation capacity of glioma cells. Taken together, these results indicate that CRLs are linked to prognosis and immune characteristics in LGG and give innovative therapeutic methods for individuals with LGG across different risk stratifications."

Biomarker • IO biomarker • Journal • Brain Cancer • Glioma • Oncology • Solid Tumor • TP63

Multi-omics profiling of ACOX3 unveils pan-cancer clinical biomarker potential. (PubMed, Comput Biol Chem) - "ACOX3 represents a dual diagnostic and prognostic biomarker with broad pan-cancer relevance, exhibiting distinct immune correlates and therapeutic potential."

Biomarker • Journal • Pan tumor • Head and Neck Cancer • Oncology • Squamous Cell Carcinoma of Head and Neck • CD4 • CD8

STARS: Safety and Tolerability of Adjunctive TBO-309 in Reperfusion for Stroke (clinicaltrials.gov) - P2 | N=80 | Recruiting | Sponsor: The Florey Institute of Neuroscience and Mental Health | Suspended ➔ Recruiting

Enrollment open • Cardiovascular • Ischemic stroke

Co-STARS: Safety, Tolerability and Efficacy of Adjunctive TBO-309 in Reperfusion for Stroke With Tandem Occlusion (clinicaltrials.gov) - P2 | N=78 | Recruiting | Sponsor: ThromBio Pty. Ltd. | Not yet recruiting ➔ Recruiting

Enrollment open • Cardiovascular • Ischemic stroke

Identification and validation of a diagnostic and prognostic model based on immune escape and cancer-associated fibroblast-related genes in lung adenocarcinoma. (PubMed, Medicine (Baltimore)) - "Kyoto Encyclopedia of Genes and Genomes analysis revealed pathways related to morphine addiction and protein digestion/absorption...Sensitivity to chemotherapeutics, such as AZD6482, ABT-263, A-770041, and BMS-536924, was observed in LUAD. Reverse transcription-quantitative polymerase chain reaction validation results demonstrated that KRT8 and S100A16 were significantly upregulated in tumor tissues, while COL4A3 and SMAD9 expression was downregulated, which was consistent with the TCGA-LUAD database analysis. In conclusion, 6 genes (KRT8, S100A16, COL4A3, SMAD9, MAP3K8, and CCDC146) were identified as potential biomarkers, offering valuable insights into LUAD pathogenesis and therapeutic strategies."

Biomarker • Journal • CNS Disorders • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Psychiatry • Solid Tumor • CD8 • MAP3K8 • S100A16 • SMAD9

Small molecule inhibitors for treating breast cancer: drug analysis based on the pathogenesis of breast cancer. (PubMed, Future Med Chem) - "Current clinical research focuses on compounds such as GDC-0077 and NVP-BKM120, advancing into phase II/III clinical trials. Preclinical drugs like NVP-CLR457, AZD6482, PF-06843195, and GDC-0326 show promising potential for further optimization and entry into BC clinical trials. This review aims to provide an overview of the clinical and preclinical development of small molecule inhibitors for various molecular subtypes of BC, emphasizing their structural composition, therapeutic outcomes, and mechanisms of action. Additionally, we highlight key targets and pathways involved in BC pathogenesis, offering essential insights for the design of effective therapeutic agents for breast cancer."

Journal • Review • Breast Cancer • Oncology • Solid Tumor

Co-STARS: Safety, Tolerability and Efficacy of Adjunctive TBO-309 in Reperfusion for Stroke With Tandem Occlusion (clinicaltrials.gov) - P2 | N=78 | Not yet recruiting | Sponsor: ThromBio Pty. Ltd. | Initiation date: May 2025 ➔ Oct 2025 | Trial primary completion date: Jun 2026 ➔ Dec 2026

Trial initiation date • Trial primary completion date • Cardiovascular • Ischemic stroke

Orphan Class A GPCRs Signature Predicts Prognosis and Immune Microenvironment in Gastric Cancer: GPR176 Drives Tumor Progression Through Wnt Signaling and Macrophage Polarization. (PubMed, Mediators Inflamm) - "Low-risk patients showed higher sensitivity to AZD6482, BX.795, GDC0941, and pazopanib. GPR176 also modulated the Wnt/β-catenin pathway and M2 macrophage polarization. These findings may provide new insights into the role of orphan class A GPR genes in STAD and identify GPR176 as a new therapeutic target for GC."

Journal • Gastric Adenocarcinoma • Gastric Cancer • Oncology • Solid Tumor • GPR176 • GPRC6A • PR176

Deciphering lactate metabolism in colorectal cancer: Prognostic modeling, immune infiltration, and gene mutation insights. (PubMed, World J Gastroenterol) - "This report underscored the pivotal mechanism of lactate metabolism in CRC prognosis and suggest novel avenues for therapeutic intervention."

Biomarker • Journal • Colorectal Cancer • Oncology • Solid Tumor

Integrated multi-omics analysis and machine learning refine molecular subtypes and clinical outcome for hepatocellular carcinoma. (PubMed, Hereditas) - "Encouragingly, we observed that the high-CMLBS patients may exhibit increased sensitivity to Alpelisib, AZD7762, BMS-536,924, Carmustine, and GDC0810, whereas they may demonstrate reduced sensitivity to Axitinib, AZD6482, AZD8055, Entospletinib, GSK269962A, GSK1904529A, and GSK2606414, suggesting that CMLBS may contribute to the selection of chemotherapeutic agents for HCC patients. Therefore, in-depth examination of data from multi-omics data can provide valuable insights and contribute to the refinement of the molecular classification of HCC. In addition, the CMLBS model demonstrates potential as a screening tool for identifying HCC patients who may derive benefit from immunotherapy, and it possesses practical utility in the clinical management of HCC."

Clinical data • Journal • Hepatocellular Cancer • Oncology • Solid Tumor

PI3Kβ inhibitor mediated immune evasion in PTEN/Trp53 double knockout prostate cancer (AUA 2025) - "Our findings suggest that PI3Kβ inhibition can effectively convert "cold" prostate cancer into immune-infiltrated ones in Pten and Trp53-deficient prostate cancer. The specific mechanism is by promoting T cell infiltration and dendritic cell maturation, while decreasing MDSC and Treg.Our study provides a strong rationale for combining AZD6482 with anti-PD-1 therapy in the treatment of PTEN and Trp53-defcient prostate cancer."

IO biomarker • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CD8 • IFNA1 • PIK3CB • PTEN • PTPRC • TP53

Construction of CD8+ T Cell-Associated Risk Model in Hepatocellular Carcinoma Based on Bulk and Single-Cell RNA-Seq Data (APASL 2025) - "BMS-754807, Gemcitabine, et al exhibited sensitive to patients in low-risk group, AZD6482 and SB505124 may serve as novel potential targeted drugs for patients in high-risk group. A CD8+ T cell-associated risk scoring model consisting of KLRB1, RGS2 and TNFRSF1B has been developed to predict prognosis and provide potential drugs for HCC treatment. Table and Figure:Figure 1."

IO biomarker • Hepatocellular Cancer • Hepatology • Oncology • Solid Tumor • CD8 • KLRB1 • RGS2 • TNFRSF1B

Co-STARS: Safety, Tolerability and Efficacy of Adjunctive TBO-309 in Reperfusion for Stroke with Tandem Occlusion (clinicaltrials.gov) - P2 | N=78 | Not yet recruiting | Sponsor: ThromBio Pty. Ltd.

New P2 trial • Cardiovascular • Ischemic stroke

A Novel Mitochondrial-Related Gene Signature for the Prediction of Prognosis and Therapeutic Efficacy in Lower-Grade Glioma. (PubMed, Biochem Genet) - "Finally, using data from the CTRPv2 and GDSC2 datasets to assess chemotherapy response in LGG, it was predicted that the chemotherapeutic agents AZD6482, MG-132, and PLX-4720 might be potential agents for patients in the high-MiAS group of LGG. In contrast, overexpression of OCIAD2 enhanced these abilities of glioma cells. This study found that MRGs were correlated with LGG patient prognosis, which is expected to provide new treatment strategies for LGG patients with different MiAS."

Gene Signature • IO biomarker • Journal • Brain Cancer • CNS Tumor • Glioma • Oncology • Solid Tumor

Machine learning-based integration develops a multiple programmed cell death signature for predicting the clinical outcome and drug sensitivity in colorectal cancer. (PubMed, Anticancer Drugs) - "In addition, the high-MPCDI group was more sensitive to AZD1332, Foretinib, and IGF1R_3801, and insensitive to AZD3759, AZD5438, AZD6482, Erlotinib, GSK591, IAP_5620, and Picolinici-acid, which suggests that the MPCDI can guide drug selection for CRC patients. As a new clinical classifier, the MPCDI can more accurately distinguish CRC patients who benefit from immunotherapy and develop personalized treatment strategies for CRC patients."

Clinical data • Journal • Machine learning • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

m6A- and m5C- modified lncRNAs orchestrate the prognosis in cutaneous melanoma and m6A- modified LINC00893 regulates cutaneous melanoma cell metastasis. (PubMed, Skin Res Technol) - "We made an analysis of m6A- and m5C- related lncRNAs in melanoma samples and a prediction of these lncRNAs' role in prognosis, tumor microenvironment, immune infiltration, and clinicopathological features. We also found that LINC00893, which is potentially regulated by m6A modification, could serve as a tumor-suppressor in melanoma and play an inhibitory role in melanoma metastasis."

Biomarker • Journal • Cutaneous Melanoma • Melanoma • Oncology • Solid Tumor • AGAP2-AS1 • METTL3 • MIAT • SEMA6A • YTHDF3

Integrated analysis of histone modification features in clear cell renal cancer for risk stratification and therapeutic prediction. (PubMed, Transl Oncol) - "Patients with low HiMG may be potential responders to rapamycin, erlotinib and FH535, while AZD6482 and CHIR-99,021 may be more suitable for patients with high HiMG levels. ccRCC histone modification distribution and a clinical signature for prognosis prediction, clinical decision making, and molecular mechanism exploration, were established for risk stratification and personalized treatments."

Epigenetic controller • IO biomarker • Journal • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Urethral Cancer • Urology • CKS2 • PD-1

Identification of a Macrophage marker gene signature to evaluate immune infiltration and therapeutic response in hepatocellular carcinoma. (PubMed, Heliyon) - "Moreover, a low-Macrosig score indicates increased sensitivity to AZD.2281, A.443654, ABT.263, ABT.888, AG.014699 and ATRA, while a high Macrosig score indicates increased sensitivity to AZD6482, AKT inhibitor VIII, AS601245, AZ628, AZD.0530 and AZD6244. A novel scoring system was constructed to guide more effective prognostic evaluation and tailoring therapeutic regimens for HCC patients."

Gene Signature • IO biomarker • Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • LAG3 • PD-1 • TIGIT

Bioinformatics Identification and Experimental Validation of a Prognostic Model for the Survival of Lung Squamous Cell Carcinoma Patients. (PubMed, Biochem Genet) - "For patients with high-risk LUSC, we discovered seven potent potential drugs (AZD6482, CHIR.99021, CMK, Embelin, FTI.277, Imatinib, and Pazopanib). In conclusion, the cuproptosis-based genes predictive risk model can be utilized to predict outcomes, track immune function, and evaluate medication sensitivity in LUSC patients."

Journal • Non Small Cell Lung Cancer • Oncology • Squamous Cell Carcinoma

SAFETY AND TOLERABILITY OF ADJUNCTIVE TBO-309 IN REPERFUSION FOR STROKE (STARS), TRIAL UPDATE (ESOC 2024) - P2 | "If the trial shows safety of the AZD6482, further trials will be conducted to assess its efficacy."

Clinical • Cardiovascular • Ischemic stroke • Thrombosis