{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Rampa DR"],"funding":["MD Anderson's Cancer Center Support Grant","Daiichi Sankyo Inc","NCI NIH HHS","AnHeart Therapeutics","The University of Hawaii Cancer Center Support Grant"],"pagination":["8896"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12469809"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["26(18)"],"pubmed_abstract":["AXL, a receptor tyrosine kinase, has emerged as a promising therapeutic target in triple-negative breast cancer (TNBC) due to its critical roles in tumor progression, metastasis, and immune evasion. In this study, we investigated the antitumor efficacy and immunomodulatory potential of AB-329, a selective AXL kinase inhibitor, in preclinical models of TNBC. Transcriptome analysis and single-cell RNA sequencing datasets revealed elevated AXL expression in mesenchymal TNBC subtypes and a negative association with immune cell infiltration. While AB-329 demonstrated moderate antiproliferative effects as a monotherapy, its combination with paclitaxel led to substantially enhanced antiproliferative and anti-metastatic effects compared to gemcitabine, DXd, and SN-38. In murine TNBC allograft models, the combination of AB-329 and paclitaxel significantly reduced tumor growth, and AB-329 increased activated natural killer (NK) cell infiltration in humanized mouse models. Analysis of human breast cancer tissue further confirmed that low AXL expression is associated with a higher presence of NK cells in the tumor. These findings suggest that AB-329 not only augments chemotherapy efficacy but also reshapes the tumor immune microenvironment, supporting its further development as a dual-action therapeutic strategy for AXL-positive TNBC."],"journal":["International journal of molecular sciences"],"pubmed_title":["Dual Therapeutic Impact of AXL Inhibitor AB-329: Chemotherapy Sensitization and Immune Microenvironment Reprogramming in TNBC."],"pmcid":["PMC12469809"],"funding_grant_id":["P30CA071789","P30CA016672","na","P30 CA016672","P30 CA071789"],"pubmed_authors":["Liu H","Fuson JA","Lee J","Qin Y","Ueno NT","Rampa DR","Pan M","Deng Y"],"additional_accession":[]},"is_claimable":false,"name":"Dual Therapeutic Impact of AXL Inhibitor AB-329: Chemotherapy Sensitization and Immune Microenvironment Reprogramming in TNBC.","description":"AXL, a receptor tyrosine kinase, has emerged as a promising therapeutic target in triple-negative breast cancer (TNBC) due to its critical roles in tumor progression, metastasis, and immune evasion. In this study, we investigated the antitumor efficacy and immunomodulatory potential of AB-329, a selective AXL kinase inhibitor, in preclinical models of TNBC. Transcriptome analysis and single-cell RNA sequencing datasets revealed elevated AXL expression in mesenchymal TNBC subtypes and a negative association with immune cell infiltration. While AB-329 demonstrated moderate antiproliferative effects as a monotherapy, its combination with paclitaxel led to substantially enhanced antiproliferative and anti-metastatic effects compared to gemcitabine, DXd, and SN-38. In murine TNBC allograft models, the combination of AB-329 and paclitaxel significantly reduced tumor growth, and AB-329 increased activated natural killer (NK) cell infiltration in humanized mouse models. Analysis of human breast cancer tissue further confirmed that low AXL expression is associated with a higher presence of NK cells in the tumor. These findings suggest that AB-329 not only augments chemotherapy efficacy but also reshapes the tumor immune microenvironment, supporting its further development as a dual-action therapeutic strategy for AXL-positive TNBC.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Sep","modification":"2026-05-02T03:20:50.344Z","creation":"2026-05-02T03:11:48.193Z"},"accession":"S-EPMC12469809","cross_references":{"pubmed":["41009462"],"doi":["10.3390/ijms26188896"]}}