ACXT-3102 / Accuronix Therap - LARVOL DELTA

Differential Sensitivity to xCT-inhibition by ME1 expression. (PubMed, Mol Cancer Ther) - "ACXT-3102 is a novel, dual-domain therapeutic produced by the conjugation of erastin, a small molecule xCT-inhibitor, and sigma-2 ligand, shown to induce ROS-dependent cell death in various cancer models...Given this differential sensitivity, ME1 deficiency may serve as a promising biomarker for selecting patients likely to benefit from xCT-targeting therapies. These results support further investigation into ME1 expression as a predictive tool for clinical trial stratification and of xCT-inhibition treatment strategies."

Journal • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • ME1

Sigma-2-Erastin inhibits PC tumor growth through lipid ROS-DUSP6-MAPK signaling (AACR 2024) - "ACXT-3102, an orally administered conjugate of sigma-2 ligand and Erastin induces PCD of human PC by uniquely regulating apoptosis and ferroptosis together. Therefore, ACXT-3102 offers a novel and improved therapeutic strategy for treating patients of fatal human carcinomas, especially those, which are difficult to diagnose at an early stage."

Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor • DUSP6 • GPX4

Trametinib Thwarts Activation of Survival Pathways Induced by Pro-ferroptotic Drug Conjugate ACXT-3102 Resulting in Enhanced Pancreatic Cancer Cell Death. (PubMed, Mol Cancer Ther) - "Our group has developed a cancer-specific drug conjugate (ACXT-3102), consisting of a proapoptotic sigma-2 ligand as a delivery moiety (SV119), linked to an inhibitor of the cystine antiporter xCT (dm-erastin), an established inducer of ferroptosis. We suspected that this was a compensatory reaction and that ACXT-3102-induced cancer cell death would be augmented by inhibition of MAPK/ERK signaling. We successfully combined ACXT-3102 with trametinib (MEK inhibitor) to enhance the overall efficacy of treatment in vitro and in vivo, presumably by targeting ACXT-3102-induced upregulation of MAPK/ERK."

Journal • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CASP3 • CASP7 • DUSP6 • GPX4

Trametinib thwarts activation of survival pathways induced by pro-ferroptotic drug conjugate ACXT-3102 resulting in enhanced pancreatic cancer cell death. (PubMed, Mol Cancer Ther) - "Our group has developed a cancer-specific drug conjugate (ACXT-3102), consisting of a pro-apoptotic sigma-2 ligand as a delivery moiety (SV119), linked to an inhibitor of the cystine antiporter xCT (dm-Erastin), an established inducer of ferroptosis. We suspected this was a compensatory reaction and that ACXT-3102-induced cancer cell death would be augmented by inhibition of MAPK/ERK signaling. We successfully combined ACXT-3102 with trametinib (MEK inhibitor) to enhance the overall efficacy of treatment in vitro and in vivo, presumably by targeting ACXT-3102-induced upregulation of MAPK/ERK."

Journal • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CASP3 • CASP7 • DUSP6 • GPX4

[VIRTUAL] Combined Inhibition of CXCR4 Signaling and System xc- Transporter Activity Induces Synthetic Lethality in T-ALL Cells By Suppressing Gsh and Inducing Ferroptosis (ASH 2020) - P2a | "Indeed, strong preclinical data demonstrating therapeutic activity of BL-8040, a potent CXCR4 antagonist, have led to a clinical trial of BL-8040 in combination with nelarabine for patients with relapsed/refractory T-ALL (NCT02763384)...Consistent with the hypothesis, treatment of T-ALL cells with ACXT-3102, a novel system xc- inhibitor, significantly enhanced BL-8040 killing of T-ALL cells in vitro. Collectively, these data suggest that T-ALL cells are sensitive to perturbations of the glutathione axis. Combined inhibition of CXCR4 signaling and system xc- activity exploits this vulnerability and presents a promising new therapeutic approach for T-ALL."

Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • Pediatrics • T Acute Lymphoblastic Leukemia • Transplantation • CASP3

Investigational drug attacks synovial sarcoma, a rare type of tumor (Washington University School of Medicine in St. Louis) - "'Synovial sarcoma is responsible for about 10% of all sarcomas, and because sarcoma in general is rare, a lot of these patients - pediatric and adult - travel from all over the country to receive treatment at our specialized Sarcoma Center,' said oncologist Brian A. Van Tine, MD, PhD..."

Media quote

Malic Enzyme 1 Absence in Synovial Sarcoma Shifts Antioxidant System Dependence and Increases Sensitivity to Ferroptosis Induction with ACXT3102. (PubMed, Clin Cancer Res) - "These findings demonstrate the translational potential of targeting redox homeostasis in ME1 null cancers, and establish the preclinical rational for a phase 1 trial of ACXT-3102 in synovial sarcoma patients."

Journal • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • ME1