OR-S1 / Daiichi Sankyo, National Cancer Center - LARVOL DELTA

EZH1/2 dual inhibitors suppress HTLV-1-infected cell proliferation and hyperimmune response in HTLV-1-associated myelopathy. (PubMed, Front Microbiol) - "Next, using an assay system that utilizes the spontaneous proliferation characteristic of peripheral blood mononuclear cells derived from patients with HAM (HAM-PBMCs), we investigated the effects of EZH2 selective inhibitors (GSK126 and tazemetostat) and EZH1/2 dual inhibitors (OR-S1 and valemetostat, also known as DS-3201), particularly on cell proliferation rate, cytokine production, and HTLV-1 proviral load. This study showed that EZH1/2 inhibitors suppress HTLV-1-infected cell proliferation through apoptosis and the hyperimmune response in HAM. This indicates that EZH1/2 inhibitors may be effective in treating HAM."

Journal • Adult T-Cell Leukemia-Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Ocular Inflammation • Oncology • Ophthalmology • Pulmonary Disease • Respiratory Diseases • Uveitis • ANXA5 • CCR4 • CD4 • CD8 • EZH2 • IFNG • IL10 • TNFA

A randomized, multi-center phase III trial of adjuvant chemotherapy with gemcitabine and capecitabine (GemCap) compared to capecitabine (Cap) alone in curatively resected biliary tract cancer (BilGemCap Study): KCSG HB20-14. (ASCO-GI 2023) - "Recent phase 3 trials using single agent such as Cap or S1 support the role of adjuvant chemotherapy as standard of care in patients with resected BTCs, but the efficacy still needs to be further improved. This is prospectively registered on ClinicalTrials.gov, NCT0005056. Clinical trial information: NCT0005056."

Clinical • P3 data • Biliary Cancer • Biliary Tract Cancer • Cholangiocarcinoma • Gallbladder Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

CDKN1C-mediated growth inhibition by an EZH1/2 dual inhibitor overcomes resistance of mantle cell lymphoma to ibrutinib. (PubMed, Cancer Sci) - "Here, we examined whether a novel inhibitor of enhancer of zeste homologs 1 and 2 (EZH1/2), OR-S1 (a close analog of the clinical stage compound valemetostat), had an antitumor effect on MCL cells...In vitro growth assays showed that compared to an established EZH2-specific inhibitor GSK126, OR-S1 had a marked antitumor effect on MCL cell lines...In addition, we identified CDKN1C (p57, KIP2), which contributes to cell cycle arrest, as a direct target of EZH1/2 and showed that its expression influenced MCL cell proliferation. These results suggest that EZH1/2 may be a potential novel target for the treatment of aggressive ibrutinib-resistant MCL via CDKN1C-mediated cell cycle arrest."

Journal • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CCND1 • EZH2