Browsing by Subject "Romidepsin"

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    A multidimensional platform of patient-derived tumors identifies drug susceptibilities for clinical lenvatinib resistance
    (Elsevier, 2024) Sun, Lei; Wan, Arabella H.; Yan, Shijia; Liu, Ruonian; Li, Jiarui; Zhou, Zhuolong; Wu, Ruirui; Chen, Dongshi; Bu, Xianzhang; Ou, Jingxing; Li, Kai; Lu, Xiongbin; Wan, Guohui; Ke, Zunfu; Medical and Molecular Genetics, School of Medicine
    Lenvatinib, a second-generation multi-receptor tyrosine kinase inhibitor approved by the FDA for first-line treatment of advanced liver cancer, facing limitations due to drug resistance. Here, we applied a multidimensional, high-throughput screening platform comprising patient-derived resistant liver tumor cells (PDCs), organoids (PDOs), and xenografts (PDXs) to identify drug susceptibilities for conquering lenvatinib resistance in clinically relevant settings. Expansion and passaging of PDCs and PDOs from resistant patient liver tumors retained functional fidelity to lenvatinib treatment, expediting drug repurposing screens. Pharmacological screening identified romidepsin, YM155, apitolisib, NVP-TAE684 and dasatinib as potential antitumor agents in lenvatinib-resistant PDC and PDO models. Notably, romidepsin treatment enhanced antitumor response in syngeneic mouse models by triggering immunogenic tumor cell death and blocking the EGFR signaling pathway. A combination of romidepsin and immunotherapy achieved robust and synergistic antitumor effects against lenvatinib resistance in humanized immunocompetent PDX models. Collectively, our findings suggest that patient-derived liver cancer models effectively recapitulate lenvatinib resistance observed in clinical settings and expedite drug discovery for advanced liver cancer, providing a feasible multidimensional platform for personalized medicine.
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    Refractory Subcutaneous Panniculitis-Like T-Cell Lymphoma with Hemophagocytic Syndrome Treated with Romidepsin and Allogeneic Hematopoietic Cell Transplantation
    (Karger, 2025-02-18) Ishizawa, Yuki; Toubai, Tomomi; Ichikawa, Tsubasa; Himuro, Masahito; Kato, Mikiya; Nagano, Yusuke; Takahashi, Ryo; Hosokawa, Masashi; Hosokawa, Yuka; Yamada, Akane; Suzuki, Takuma; Aizawa, Keiko; Ito, Satoshi; Peltier, Daniel; Yokoyama, Hisayuki; Ishizawa, Kenichi; Pediatrics, School of Medicine
    Introduction: Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare subtype of cutaneous T-cell lymphoma (CTCL) that when refractory or complicated by hemophagocytic syndrome (HPS) has a poor prognosis. Romidepsin is a histone deacetylase inhibitor, but its efficacy for SPTCL is unknown. The efficacy of allogeneic hematopoietic cell transplantation (allo-HCT) is also unclear. Herein, we report a case of refractory SPTCL with HPS that was successfully treated with romidepsin followed by consolidation with allo-HCT. Case presentation: A 26-year-old female presented with fever, generalized painful erythema, pancytopenia, and hemophagocytosis. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET) showed diffuse PET-avid infiltration of the subcutaneous adipose tissue found to be SPTCL via skin biopsy. Her SPTCL was refractory to conventional chemotherapy but complete metabolic response was achieved after romidepsin. An allo-HCT was used for consolidation, and she remains in complete remission 3 years later. Conclusion: Romidepsin with allo-HCT consolidation may be an effective approach for refractory SPTCL.