Introduction: Nuclear protein in testis midline carcinoma (NMC) is a rare and extremely aggressive carcinoma (median survival Case Report: A 61-year old female NMC patient enrolled on study CUDC-907-102 (NCT02307240) ...Introduction: Nuclear protein in testis midline carcinoma (NMC) is a rare and extremely aggressive carcinoma (median survival Case Report: A 61-year old female NMC patient enrolled on study CUDC-907-102 (NCT02307240) after rapidly progressing through two prior treatments. The patient’s assessable sites of disease consisted of right pleural effusion, right hilar soft tissue, and segment IV liver. Treatment was well tolerated with toxicities primarily consisting of manageable diarrhea and thrombocytopenia. The patient remains on active treatment after more than 32 months of stable disease. Discussion: Dysregulation of MYC in NMC is believed to play a central role in pathogenesis. CUDC-907 has demonstrated potent suppression of MYC expression and anti-tumor activity in preclinical NMC models, providing a mechanistic rationale for the prolonged disease stabilization observed here. The treatment of additional NMC patients with CUDC-907 is needed to further evaluate this promising report. Conclusion: This case demonstrates a rare success in the treatment of a devastating disease using only a novel small molecule, warranting further investigation of CUDC-907 in NMC.展开更多
MEF2D fusions are found in a special subtype of B-cell precursor acute lymphoblastic leukemia(BCP-ALL)with poor prognosis.In this study,we conducted high-throughput drug screenings using cell line and ex vivo cell mod...MEF2D fusions are found in a special subtype of B-cell precursor acute lymphoblastic leukemia(BCP-ALL)with poor prognosis.In this study,we conducted high-throughput drug screenings using cell line and ex vivo cell model harboring,respectively,MEF2D::HNRNPUL1(MH)and MEF2D::BCL9(MB),the two major MEF2D fusions.We identified CUDC-907 as a highly potent dual-target inhibitor of PI3K/HDAC,demonstrating remarkable efficacy in inducing robust lethality while maintaining selectivity for MEF2D fusion-expressing cells.CUDC-907 effectively induced apoptosis and promoted the down-regulation of pre-BCR signaling.We discovered that the hyperactivation of the PI3K-AKT signaling pathway,HDAC9,and BCL2 contributed to the sustained state of MEF2D fusion(+)BCP-ALL.展开更多
文摘Introduction: Nuclear protein in testis midline carcinoma (NMC) is a rare and extremely aggressive carcinoma (median survival Case Report: A 61-year old female NMC patient enrolled on study CUDC-907-102 (NCT02307240) after rapidly progressing through two prior treatments. The patient’s assessable sites of disease consisted of right pleural effusion, right hilar soft tissue, and segment IV liver. Treatment was well tolerated with toxicities primarily consisting of manageable diarrhea and thrombocytopenia. The patient remains on active treatment after more than 32 months of stable disease. Discussion: Dysregulation of MYC in NMC is believed to play a central role in pathogenesis. CUDC-907 has demonstrated potent suppression of MYC expression and anti-tumor activity in preclinical NMC models, providing a mechanistic rationale for the prolonged disease stabilization observed here. The treatment of additional NMC patients with CUDC-907 is needed to further evaluate this promising report. Conclusion: This case demonstrates a rare success in the treatment of a devastating disease using only a novel small molecule, warranting further investigation of CUDC-907 in NMC.
基金supported by research grant 82230006,82300167 from the National Natural Science Foundation of Chinathe Overseas Expertise Introduction Project for Discipline Innovation(111 Project,B17029)+4 种基金Shanghai Shenkang Hospital Development Center(No.SHDC2020CR5002)Innovative Research Team of High-level Local Universities in Shanghai,CAMS Innovation Fund for Medical Sciences(CIFMS 2021-I2M-5-010)Yangfan Special Project of Shanghai Science and Technology Innovation Action Plan(23YF1424300)National Key Research and Development Program of China(No.2023YFC2508900)Science and Technology Commission of Shanghai Municipality(No.23141903000).
文摘MEF2D fusions are found in a special subtype of B-cell precursor acute lymphoblastic leukemia(BCP-ALL)with poor prognosis.In this study,we conducted high-throughput drug screenings using cell line and ex vivo cell model harboring,respectively,MEF2D::HNRNPUL1(MH)and MEF2D::BCL9(MB),the two major MEF2D fusions.We identified CUDC-907 as a highly potent dual-target inhibitor of PI3K/HDAC,demonstrating remarkable efficacy in inducing robust lethality while maintaining selectivity for MEF2D fusion-expressing cells.CUDC-907 effectively induced apoptosis and promoted the down-regulation of pre-BCR signaling.We discovered that the hyperactivation of the PI3K-AKT signaling pathway,HDAC9,and BCL2 contributed to the sustained state of MEF2D fusion(+)BCP-ALL.
