AZD8055 / AstraZeneca - LARVOL DELTA

A prognostic glycolysis-related gene signature in osteosarcoma: implications for metabolic programming, immune microenvironment, and drug response. (PubMed, PeerJ) - "Moreover, a significant disparity in drug sensitivity to AZD8055, paclitaxel, and PD0325901 was noted between the high-risk and low-risk cohorts, and the established four-gene risk signature served as dependable prognostic indicators in the validation cohort, confirmed at the cellular level through external dataset validation and reverse transcription quantitative PCR (RT-qPCR) experiments. A risk signature based on GRGs was established for OS, exhibiting robust predictive efficacy for prognostic assessment, and offering significant clinical utility for the prognosis of OS."

Biomarker • Gene Signature • Journal • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • RAS • RRAGD • TPR • VCAN

NF1 mutations in lung adenocarcinoma preclinical models and potential targeted therapies: The crucial role of the RAS-MAPK pathway (AACR 2025) - "No sensitivity was observed in these models when treated with the mTOR inhibitor AZD8055 or the PI3K inhibitor Buparlisib alone. We then performed in vivo pharmacological tests on the LUAD PDX: Trametinib alone and in combination with Buparlisib resulted in significant tumor volume reductions of 72% and 84%, respectively. Collectively, these findings establish a promising possible efficacy of MEK inhibitors for LUAD patients with NF1 homozygous mutation."

Preclinical • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS • NF1

Single cell fixed RNA-seq revealed HSCLMCD1+LIMK2+ is a driver of liver fibrosis by modulating SMAD3-AKT-PRAS40-4EBP1 (EASL 2025) - "Specific inhibition using AZD8055 mitigated HSC activation, both spontaneously and under TGF-β stimulation, and significantly reduced the phosphorylation of 16/39 proteins implicated in HSC activation, including CREB, c-JUN, TP53, WNK1, GSK3B, STAT2/3, HSP27/60, and RSK1/2/3... This study highlights previously unrecognized molecular and cellular dynamics of HSCs, identifying LMCD1 and LIMK2 as promising therapeutic targets for antifibrotic interventions."

Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Metabolic Dysfunction-Associated Steatotic Liver Disease • AKT1S1 • EIF4EBP1 • ETV4 • FOSL1 • GATA2 • GATA3 • JUN • PDLIM5 • PDLIM7 • SMAD3 • STAT2 • TGFB1 • TP53 • UNC13D • VIM • WNK1

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

The miR-451a facilitates natural killer cell-associated immune deficiency after ischemic stroke. (PubMed, J Cereb Blood Flow Metab) - "Pharmacological inhibition of Akt-mTOR pathway with AZD8055 effectively blocked the impacts of miR-451a on NK cell functions. Collectively, these findings suggest miR-451a negatively regulates NK cell cytotoxicity in both the brain and periphery, which could be re-addressed by modulating the Akt-mTOR signaling pathway."

Journal • Cardiovascular • CNS Disorders • Infectious Disease • Inflammation • Ischemic stroke • CD69 • IFNG • MIR451A

Silencing fatty acid-binding protein 4 improved sepsis-induced myocardial dysfunction through anti-apoptotic and antioxidant effects by mammalian target of rapamycin signaling pathway. (PubMed, Cytojournal) - "However, the therapeutic effect was inhibited when FABP4 silencing was combined with the mTOR inhibitor AZD-8055. Silencing FABP4 alleviates LPS-induced inflammatory response and apoptosis in H9c2 cells and enhances mitochondrial function through the mTOR signaling pathway."

IO biomarker • Journal • B Cell Lymphoma • Infectious Disease • Lymphoma • Oncology • Septic Shock • BAX • FABP4

An mTOR inhibitor discovery system using drug-sensitized yeast. (PubMed, Geroscience) - "Inhibition of the target of rapamycin (TOR/mTOR) protein kinase by the drug rapamycin extends lifespan and health span across diverse species...In contrast, 100 nM Torin1 and 500 nM GSK2126458 (omipalisib) are sufficient to identify TOR1-dependent growth inhibition in the drug-sensitized background...Additionally, for the TOR inhibitor AZD8055, the drug-sensitive system resolves that the compound results in TOR1-dependent growth sensitivity at 100 µM, whereas no growth inhibition is observed in a wild-type yeast strain background. Our platform also identifies the caffeine analog aminophylline as a TOR1-dependent growth inhibitor via selective tor1 growth sensitivity. We also tested nebivolol, isoliquiritigenin, canagliflozin, withaferin A, ganoderic acid A, and taurine and found no evidence for TOR inhibition using our yeast growth-based model. Our results demonstrate that this system is highly effective at identifying compounds that inhibit the TOR..."

Journal • Oncology

Identification of cuproptosis and ferroptosis-related subtypes and development of a prognostic signature in colon cancer. (PubMed, PLoS One) - "AZD8055_1059, Bortezomib_1191, Dihydrorotenone_1827, and MG-132_1862 were more sensitive in the high-risk group. Finally, we analyzed differential expression of model-related genes between tumor tissues and normal tissues, validated through real-time quantitative PCR and immunohistochemistry. In summary, our study provides a relatively accurate prognostic tool for colon cancer patients, offering guidance for treatment selection and indicating the potential of immunotherapy in colon cancer."

Biomarker • IO biomarker • Journal • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor

Glioma-induced alterations in excitatory neurons are reversed by mTOR inhibition. (PubMed, Neuron) - "A single acute dose of AZD8055, a combined mTORC1/2 inhibitor, reversed these tumor-induced changes. These findings reveal mTOR-driven pathological plasticity in neurons at the infiltrative margin of glioma and suggest new strategies for treating glioma-associated neurological symptoms."

Journal • Brain Cancer • CNS Disorders • CNS Tumor • Cognitive Disorders • Epilepsy • Glioma • Oncology • Solid Tumor

An integrated machine learning framework for developing and validating a prognostic risk model of gastric cancer based on endoplasmic reticulum stress-associated genes. (PubMed, Biochem Biophys Rep) - "Moreover, five specific targeted therapy drugs, namely BMS-754807, Dasatinib, JQ1, AZD8055 and SB505124, produced better results in the treatment of the high-risk group of patients. A new molecular prognostic model associated with ERS was established and validated for GC and showed relatively good discriminative and predictive ability. This model greatly expands the collection of weapons in the armoury of prognostic analysis in GC."

IO biomarker • Journal • Machine learning • Gastric Cancer • Oncology • Solid Tumor

ADAM15 as a potential biomarker for pan-cancer prognosis and immunotherapy: Validation in HCC (ESMO Asia 2024) - "Drug sensitivity analysis revealed a positive correlation and significant change of gene with AZD-8055 and Nitazoxanide, negative correlation with Oxaliplatin and Ponatinib, which was confirmed by molecular docking. Conclusions ADAM15 may exert a significant influence on cancer development, prognosis, and susceptibility to therapy. In addition, it may serve as a potential prognostic and immunological pan-cancer biomarker."

Biomarker • IO biomarker • Pan tumor • Hepatocellular Cancer • Oncology • ADAM15

TOR Inhibition Enhances Autophagic Flux and Immune Response in Tomato Plants Against PSTVd Infection. (PubMed, Physiol Plant) - "In this study, we have investigated the role of the Target Of Rapamycin (TOR) signaling pathway in modulating viroid pathogenesis in tomato plants infected with PSTVd...Pharmacological inhibition of TOR with AZD8055 mitigated PSTVd symptomatology by reducing viroid accumulation...It primed the plant defense response, as evidenced by enhanced expression of the defense-related gene PR1b and S5H, a gene involved in the salicylic acid catabolism. These results suggest a novel role for TOR in regulating viroid-induced pathogenesis and highlight the potential of TOR inhibitors as tools for enhancing plant resistance against viroid infections."

Journal • Infectious Disease

AZD8055 Is More Effective Than Rapamycin in Inhibiting Proliferation and Promoting Mitochondrial Clearance in Erythroid Differentiation. (PubMed, Anal Cell Pathol (Amst)) - " AZD8055 is more effective than rapamycin in inhibiting proliferation and promoting mitochondrial clearance in erythroid differentiation, which might provide us one more therapeutic option other than rapamycin for ineffective erythropoiesis treatment in the future. These findings also provide some preliminary information indicating the roles of mTORC1 and mTORC2 in erythropoiesis, and further studies are necessary to dissect the underlying mechanisms."

Journal • Beta-Thalassemia • Genetic Disorders • Hematological Disorders • GYPA

Screening of potential targets and small-molecule drugs related to lipid metabolism in ovarian cancer based on bioinformatics. (PubMed, Biochem Biophys Res Commun) - "six OC potential genes related to lipid metabolism were identified and verified, which can be used as potential biomarkers and therapeutic targets to evaluate the prognostic risk of OC patients. In addition, three small-molecular drugs that may be effective in the treatment of OC were unearthed, among which Cephaeline has the most potential. We speculate that Cephaeline may target six genes to inhibit progression of OC by affecting lipid metabolism."

Journal • Metabolic Disorders • Oncology • Ovarian Cancer • Solid Tumor • CPT1A

Reversing oxidative stress-induced senescence in small airway epithelial cells using the mTOR inhibitor AZD8055 (ERS 2024) - "Direct inhibition of mTOR via AZD8055 reverses oxidative-stress induced senescence in SAECs. Further investigation into the effect of AZD8055 on SIRT1 activity will help confirm a direct interaction on SIRT1."

Oxidative stress • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases • CDKN1A • CXCL8

Target of rapamycin coordinates auxin are involved in exogenous melatonin regulated low temperature tolerance in cucumber seedlings. (PubMed, Plant Physiol Biochem) - "In addition, co-treatment with AZD-8055 (a TOR inhibitor) or NPA (N-1-naphthylphthalamic acid, an auxin polar transport inhibitor) and MT attenuated MT-induced resistance to LT stress, leading to higher levels of reactive oxygen species (ROS), reduced antioxidant defense capacity, and increased damage to the membrane system in cucumber seedlings. In summary, the present study demonstrates that TOR and auxin signaling synergistically contribute to alleviating LT damage in cucumber seedlings by exogenous MT. These findings help us understand the function of MT and provide insights into the regulatory network of MT that regulates the LT tolerance of plants."

Journal • PIN1

Tristetraprolin mediates immune evasion of mycobacterial infection in macrophages. (PubMed, FASEB Bioadv) - "Rapamycin and AZD8055 specifically blocked 4EBP1 phosphorylation in infected macrophages and suppressed intracellular BCG growth. Rapamycin promoted TTP protein degradation through the ubiquitination pathway, whereas the proteasome inhibitor MG-132 blocked rapamycin function and thus stabilized TTP protein...Moreover, blocking TTP binding increased the expression of TNF-α and iNOS and suppressed intracellular mycobacterial growth. Overall, our study reveals a novel role for RNA-binding protein TTP in Mtb immune evasion mechanisms and provides a potential target for host-directed therapy against tuberculosis (TB)."

Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Targeted Protein Degradation • Tuberculosis • EIF4EBP1 • IL12A • IL23A • TNFA

Comprehensive analysis of CPNE1 predicts prognosis and drug resistance in gastric adenocarcinoma. (PubMed, Am J Transl Res) - "CPNE1 could be a predictive biomarker and a potential target for biological therapy in STAD."

Journal • Gastric Adenocarcinoma • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CPNE1

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

Dissecting gastric cancer heterogeneity and exploring therapeutic strategies using bulk and single-cell transcriptomic analysis and experimental validation of tumor microenvironment and metabolic interplay. (PubMed, Front Pharmacol) - "Despite resistance to immunotherapy, the high-risk group showed sensitivity to molecular targeted agents directed at IGF-1R (BMS-754807) and the PI3K-mTOR pathways (AZD8186, AZD8055). This study unveils the intricate interplay between TME and metabolic pathways in gastric cancer, offering potential for enhanced diagnosis, patient stratification, and personalized treatment. Understanding molecular features in each subtype enriches our comprehension of gastric cancer heterogeneity and potential therapeutic targets."

Biomarker • Heterogeneity • IO biomarker • Journal • Tumor microenvironment • Gastric Cancer • Gastrointestinal Cancer • Microsatellite Instability • Oncology • Solid Tumor • CD36 • KYNU • MSI • SCARB1

CPT1A loss disrupts BCAA metabolism to confer therapeutic vulnerability in TP53-mutated liver cancer. (PubMed, Cancer Lett) - "Consistently, Cpt1a loss in HCC directs tumor cell therapeutic response to AZD-8055. Our results show genetic evidence for CPT1A as a metabolic tumor suppressor in HCC and provide a therapeutic approach for TP53 mutant HCC patients."

Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Metabolic Disorders • Oncology • Solid Tumor • CPT1A • TP53

mTORc2 in Distal-Convoluted-Tubule and Renal K+-Excretion during High Dietary K+ Intake. (PubMed, J Am Soc Nephrol) - "mTORc2 of the DCT inhibits Kir4.1/Kir5.1 activity and NCC expression, and stimulates renal-EK during high-K+-intake."

Journal • DCT • RICTOR

Cucumber (Cucumis sativus L.) translationally controlled tumor protein interacts with CsRab11A and promotes activation of target of rapamycin in response to Podosphaera xanthii. (PubMed, Plant J) - "The target of rapamycin (TOR) kinase serves as a central regulator that integrates nutrient and energy signals to orchestrate cellular and organismal physiology in both animals and plants. Moreover, our findings demonstrate that the critical role of TOR in plant disease resistance is contingent upon its regulated activity; pretreatment with a TOR inhibitor (AZD-8055) enhances cucumber plant resistance to P. xanthii, while pretreatment with a TOR activator (MHY-1485) increases susceptibility. These results suggest a sophisticated adaptive response mechanism in which upstream regulators, CsTCTP and CsRab11A, coordinate to modulate TOR function in response to P. xanthii, highlighting a novel aspect of plant-pathogen interactions."

Journal • Oncology

Exploring the association between miR-9-5p levels and the mTORC1/mTORC2 pathway in laryngeal cancer cell lines (AACR 2024) - "Background: We previously demonstrated that differing levels of miR-9-5p could predict chemosensitivity to cisplatin, and that miR-9-5p is a regulator of potential chemotherapeutic target MAP1B...The IC50 of an mTORC1 inhibitor (Rapamycin) and an mTORC1/C2 inhibitor (AZD-8055) were evaluated using the Cell Titer Blue Viability assay. Cells were treated with the de-methylating agent, 5-Azacytidine (1μM)... In conclusion, our study suggests that miR-9-5p may regulate MAP1B gene expression via the mTORC2 pathway. In addition, methylation may play a role in the regulation of the miR-9-5p gene and its downstream targets in laryngeal cancer tumorigenesis. Future studies will involve exploring epigenetic mechanisms of miR-9-5p inhibition and defining the role of key mediators of the mTOR pathway in LSCC."

Preclinical • Head and Neck Cancer • Laryngeal Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • EGFR • MAP1B • PIK3CA • PTEN

Chemically engineered mTOR-nanoparticle blockers enhance antitumour efficacy. (PubMed, EBioMedicine) - "The mTOR inhibition by chemically engineered nanoblocker presented here had enhanced efficacy against tumours compared with the pristine drug and thus has the potential to improve the survival outcomes of patients with HCC. Additionally, this new nanosystem derived from co-assembling of small-molecule prodrug entities can serve as a delivery platform for the synergistic co-administration of distinct pharmaceutical agents."

Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Infectious Disease • Liver Cancer • Oncology • Solid Tumor • CD8 • IFNG