AZD8055 / AstraZeneca - LARVOL DELTA

The mTORC1/2 Inhibitor AZD-8055 Significantly Inhibits Metabolism and Metastatic Potential in Lenvatinib Resistant Thyroid Cancer (ATA 2026) - No abstract available

Metastases • Oncology • Solid Tumor • Thyroid Gland Carcinoma

Deciphering the Dysregulated Pathways and Candidate Therapeutic Compounds for Primary Ovarian Cancer Using Whole Transcriptomics Data and Next Generation Knowledge Discovery Strategies. (PubMed, J Cell Mol Med) - "Based on NGKD analysis, we identified approximately 50 synthetic or natural compounds, including naproxol, palbociclib, etoposide, wortmannin, PP-110, AZD-8055, amsacrine and BRD-K6595526. The results of this study could aid in the development of personalized treatment plans based on the unique profile of each tumour type, thus facilitating the development of personalized or precision treatment plans and improving diagnostic and prognostic capabilities in the clinic. In conclusion, the combination of RNA-seq and cutting-edge NGKD methodologies holds significant promise for identifying key cellular and molecular pathways and OC therapeutics."

IO biomarker • Journal • Epithelial Ovarian Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor • TGFB1

Dopamine triggers TOR signaling cascade to drive biomass and astaxanthin hyperaccumulation in Haematococcus lacustris under coordinated salinity and gradient light stress. (PubMed, Bioresour Technol) - "DA upregulated the astaxanthin biosynthesis genes but downregulated the autophagy-related gene ATG8, whereas AZD8055 treatment produced the opposite effects on these genes. These findings indicate a promising and effective biotechnological strategy that combines DA, gradient light, and salinity stress to boost biomass and astaxanthin production, and further suggest that the promotive effects of DA on astaxanthin accumulation and stress resistance are associated with TOR-related signaling."

Journal

AI-driven structure- and ligand-based discovery of novel Ferrochelatase inhibitors from heterocyclic libraries. (PubMed, J Mol Graph Model) - "Ultimately, this study demonstrates the immense utility of constructing an integrated, AI-driven structure- and ligand-based workflow to explore FECH inhibitors. By successfully identifying AZD-8055 and hSMG-1 inhibitor 11e as potential FECH inhibitors in silico, this approach provides a strong theoretical foundation for the development of dual-modality photodynamic and anti-angiogenic therapeutics."

Journal

From Single-cell Insights to Clinical Relevance: An M2 Macrophagebased Prognostic Model for Osteosarcoma. (PubMed, Curr Med Chem) - "This study developed an M2 macrophage-related four-gene model that was closely related to the immune microenvironment features, drug sensitivity, and survival outcomes in OS. These findings offer preliminary insights into risk stratification and therapeutic treatment for OS."

Journal • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • LPAR5 • TNFSF8

MET-associated immune prognostic signature predicts survival and guides personalized therapy in glioma. (PubMed, Acta Neuropathol Commun) - "Bioinformatic prediction and patient-derived organoid assays verified that low-MIPS tumors were sensitive to multiple targeted drugs (e.g., Axitinib, AZD-8055, Gefitinib, and Lenalidomide), while high-MIPS tumors were relatively resistant. MIPS derived from MET alteration serves as a robust biomarker for prognosis and predictive tool for immunotherapy and chemotherapy, facilitating patient stratification and precision therapy."

IO biomarker • Journal • Brain Cancer • Glioma • Oncology • Solid Tumor • CD276 • MET

Pharmacogenomic characterization of a uric acid metabolism-related signature associated with prognosis and drug sensitivity in gastric cancer. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "Drug sensitivity prediction showed lower predicted half-maximal inhibitory concentration (IC50) values for selected agents, including AZD8055, in the high-risk subgroup, suggesting a potential association with pharmacogenomic drug-response patterns...RT-qPCR confirmed downregulation of ABCG4 and GPX3 and upregulation of SERPINE1 in GC cell lines. These findings identified prognostic features associated with uric acid metabolism in gastric cancer and suggest that ABCG4, SERPINE1, and GPX3 may be involved in metabolic dysregulation, matrix remodeling, and predicted pharmacogenomics response patterns."

Biomarker • Journal • Gastric Cancer • Metabolic Disorders • Oncology • Solid Tumor • SERPINE1

Inhibition of mTOR Signaling Suppresses Growth and Downregulates Oxidative Phosphorylation of Lenvatinib Resistant Thyroid Cancer (ENDO 2026) - "The high throughput screening studies suggested AZD-8055, a strong mTORC1/2 inhibitor, as an effective agent inhibiting growth of LR clones with a delta AUC between LS and LR cells of 138.46. LR TC is characterized by altered metabolism with significantly increased mitochondrial respiration. Targeting mTOR pathway leads to inhibition of growth and mitochondrial respiration of LR TC and can be a promising strategy to overcome resistance."

Oncology • Solid Tumor • Thyroid Gland Carcinoma • ABCB1

Patient-derived organoids guide personalized therapy for KRAS-mutant pancreatic cancer: synergistic MEK/mTOR inhibition and predictive chemotherapy responses. (PubMed, Front Immunol) - "The synergistic effects of the MEK inhibitor trametinib combined with the mTOR inhibitor AZD8055 or the pan-CDK inhibitor flavopiridol were evaluated in PDOs and validated in matched PDXs. We also validated PDOs in predicting clinical gemcitabine/paclitaxel (Gem/PTX) responses...The trametinib/AZD8055 combination is a promising precision therapeutic strategy, and PDOs can serve as a reliable tool to guide clinical therapy selection. Despite limitations such as small sample size, lack of tumor microenvironment and immune components in the model system, this work provides important preclinical evidence for the clinical translation of PDOs in the personalized therapy of PDAC."

Journal • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CA 19-9 • KRAS

Identification of prognostic genes and development of a risk model for pancreatic cancer based on hypoxia- and lipid metabolism-related genes. (PubMed, Discov Oncol) - "INPP4B, SLCO1B3, LIPH, TGM2, ACSL5, SLC2A1, and EPHX2 were identified as hypoxia- and lipid metabolism-related prognostic genes in PC. Distinct immune cell subsets were also characterized during PC progression. These findings provide a foundation for further mechanistic studies and potential prognostic applications."

Journal • Metabolic Disorders • Oncology • Pancreatic Cancer • Solid Tumor • ACSL5 • CD4 • INPP4B • LIPH • SLC2A1 • SLCO1B3 • TGM2

Leveraging mitochondrial dynamics-related risk signatures to predict the prognosis and tumor microenvironment of lung adenocarcinoma. (PubMed, Discov Oncol) - "This work set up a prognostic model for LUAD based on 8 MDRGs, pinpointing promising biomarkers and targets for LUAD treatment."

Biomarker • Journal • Tumor mutational burden • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CYP27A1 • HMGA2 • SLC2A3 • TMB

ET-resistant cell populations in ER positive breast cancer: From profiling to therapeutic targeting (AACR 2026) - "Leveraging single cell RNA sequencing data from the FELINE clinical trial, we profiled tumors from nine ER+ breast cancer patients treated with letrozole at baseline and after 14 days of therapy...Using a novel predictive therapeutic pipeline that integrates transcriptional profiling with drug response modeling on PDxOs, we identified and validated candidate drugs targeting both shared and patient-specific ET-resistant populations, including known drugs already used in clinic, such as dasatinib, as well as novel compounds such as pluripotin and AZD8055...Our integrated framework allowed us to uncover both patient-specific and shared ET-resistant cell populations, and to test personalized therapeutic strategies for targeting ET resistance. Together, our findings reveal a complex and heterogeneous landscape of endocrine therapy response, highlighting the critical importance of single-cell resolution to inform therapeutic strategies aimed at overcoming resistance and..."

Clinical • Breast Cancer • Estrogen Receptor Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER

Lack of Kir4.1 in the Distal Convoluted Tubule Causes ENaC Hyperactivity During K+ Restriction Leading to Hypokalemia. (PubMed, Acta Physiol (Oxf)) - "We conclude that Kir4.1 deletion drives ENaC hyperactivity in the DCT via the mTORC2-dependent SGK1/Nedd4-2 signaling pathway, promoting low potassium diet-induced hypokalemia."

Journal • NEDD4

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

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

Glutamine alleviates the toxicity of externally applied amino acids in Arabidopsis. (PubMed, Front Plant Sci) - "The involvement of Target of Rapamycin (TOR) was tested using the specific inhibitor AZD8055. TOR inhibition completely overrode the toxicity of Val and masked the effects of Gln, in good agreement with TOR being a high order regulator of the metabolism, but precluding any conclusion as to whether it is involved in the Gln-suppressing effect of Val toxicity."

Journal

Epigenetic Activity of Cancer Therapy Drugs Revealed by HeLa TI Cell-Based Assay. (PubMed, Epigenomes) - "Our findings show that many anticancer therapy agents modulate the epigenetic landscape of cancer cells, providing a rationale for expanding their therapeutic applications and enhancing the efficacy of combination strategies by overcoming epigenetically driven chemoresistance."

IO biomarker • Journal • Oncology

HYPOKALEMIA IN EAST/SESAME SYNDROME: POTENTIAL ROLE OF MTOR PATHWAY (ISN-WCN 2026) - "Amiloride treatment induced similar natriuresis and kaliuresis in DCT-Kir4.1 KO and kidney-specific Kir4.1 KO mice, but had minimal effects in collecting system Kir4.1 KO mice, suggesting enhanced ENaC activity following Kir4.1 deletion in the DCT...Inhibition of mTOR with AZD8055 reduced SGK1/Nedd4-2 phosphorylation, cleaved α-ENaCexpression, and DCT2 ENaC currents, suggesting a role for mTOR in ENaC hyperactivity in K+-restricted DCT-Kir4.1 KO mice. This notion was also supported by observations that Rictor staining was significantly upregulated in the isolated DCT of these KO mice. Furthermore, the mTORC2 inhibitor JR-AB2-011 abolished elevated DCT2 ENaC currents in NPPB-treated isolated DCTs from both WT and KO mice.Conclusion We conclude that Kir4.1 deletion drives ENaC hyperactivity in the DCT via the Cl--dependent mTORC2/SGK1/Nedd4-2 signaling pathway, promoting low potassium diet-induced hypokalemia."

Metabolic Disorders • NEDD4

ULK1 promotes metastatic progression in experimental models of epithelial ovarian cancer. (PubMed, Oncogene) - "To investigate this, we utilized CRISPR/Cas9 technology to delete ULK1 in EOC cell lines OVCAR8, HEYA8, ES2 and the fallopian tube epithelial cell line FT190. Treatment of metastatic patient-derived organoids with the clinical ULK1 inhibitor DCC-3116, MEK inhibitor trametinib, or mTORC1/2 inhibitor AZD-8055 reduced viability in a subset of these samples, reflecting inter-patient heterogeneity and need for biomarker-guided selection. Overall, this study highlights ULK1 as a critical regulator of multiple steps of EOC disease progression, underscoring its potential as a therapeutic target in advanced ovarian cancer."

Journal • Epithelial Ovarian Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor • BECN1 • ULK1

ADAM15 Is a Potential Biomarker for Pan-Cancer Prognosis and Immunotherapy: Validation in HCC and COAD. (PubMed, IUBMB Life) - "Drug sensitivity profiling unveiled a positive and statistically significant association between ADAM15 and AZD-8055 and Nitazoxanide, whereas a negative correlation was observed with Oxaliplatin and Ponatinib. Our study underscores the multifaceted role of ADAM15 in cancer progression, immune evasion, and response to therapy. By elucidating the intricate interplay between ADAM15 and the tumor microenvironment (TME), we have identified novel diagnostic biomarkers and potential therapeutic avenues."

Biomarker • IO biomarker • Journal • Pan tumor • Colon Adenocarcinoma • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Hepatocellular Cancer • Immune Modulation • Immunology • Oncology • Solid Tumor • ADAM15

Functional characterisation of Target of Rapamycin (TOR) signalling in Physcomitrella. (PubMed, Plant Cell Rep) - "Likewise, protonema growth was inhibited when the TOR-specific inhibitor AZD8055 was present in the culture. Collectively, our results show that Physcomitrella growth and development is positively controlled by a conserved TOR kinase. We suggest to further dissect TOR signalling in Physcomitrella in order to elucidate signalling integration via TORC1 in plants."

Journal • FKBP5 • RICTOR • RPS6

United multi-omics and machine learning refine regulatory T cell-defined hepatocellular carcinoma subtypes. (PubMed, iScience) - "The high-risk group may be effective against the mTOR inhibitor AZD8055. Comprehensive multi-omics data and multiple ML algorithms offer key insights into HCC occurrence and evolution, with model scores guiding patient prognosis and treatment clinically."

IO biomarker • Journal • Hepatocellular Cancer • Oncology • Solid Tumor

Targeting tumour-astrocyte crosstalk for rational identification of novel therapeutic targets for medulloblastoma and atypical teratoid/ rhabdoid tumours (SNO 2025) - "3D migration studies found that T-5224 (FOS inhibitor) and AZD8055 significantly reduced migration of spheroids in vitro for MB cells.Delivery of T-5224 and AZD8055 to a d425 resection model demonstrated tolerability. Similarly, delivery of Tiplaxtinin and AZD8055 conferred tolerability in a BT12 resection model and a survival advantage was indicated in groups treated with AZD8055 alone."

Brain Cancer • Medulloblastoma • Oncology • Rhabdoid Tumor • Sarcoma • Solid Tumor • COL1A1 • MMP2 • NOTCH3 • S100A10 • SERPINE1 • SOCS3 • TGFBR2

Treatment with L-type amino acid transporter 1 inhibitor JPH203 enhances protein synthesis in C2C12 myotubes. (PubMed, Sci Rep) - "ATP-competitive mTOR inhibitor AZD8055 (1 μM) suppressed JPH203-induced protein synthesis. JPH203 treatment increased intracellular glutamine concentration. These results suggest that inhibition of LAT1 function augments muscle protein synthesis, possibly through the activation of rapamycin-insensitive mTOR signaling; elevated intracellular glutamine levels may contribute to the enhancement of muscle protein synthesis induced by LAT1 inhibition."

Journal • EIF4EBP1

Targeting tumour-astrocyte crosstalk for rational identification of novel therapeutic targets for medulloblastoma and atypical teratoid/ rhabdoid tumours (WFNOS 2025) - "3D migration studies found that T-5224 (FOS inhibitor) and AZD8055 significantly reduced migration of spheroids in vitro for MB cells.Delivery of T-5224 and AZD8055 to a d425 resection model demonstrated tolerability. Similarly, delivery of Tiplaxtinin and AZD8055 conferred tolerability in a BT12 resection model and a survival advantage was indicated in groups treated with AZD8055 alone."

Brain Cancer • Medulloblastoma • Rhabdoid Tumor • Sarcoma • Solid Tumor • COL1A1 • MMP2 • NOTCH3 • S100A10 • SERPINE1 • SOCS3 • TGFBR2