Amsidine (amsacrine)

P2/3, N=745, Completed, Universitätsklinikum Hamburg-Eppendorf | Active, not recruiting --> Completed

The dysregulation of microRNAs and transcription factors adds complexity to ACC's molecular profile. Exploration of drug-gene interactions reveals promising therapeutic strategies, involving FDA-approved drugs such as amsacrine and rucaparib, providing avenues for personalized interventions.

05 and absolute log2FC>1) in the high-resistance group for one or multiple drugs: amsacrine (ams, n = 10), etoposide (eto, n = 10), tioguanine (thio, n = 8) and mitoxantrone (mito, n = 1). Importantly, our analysis indicates that the differential expression of snoRNAs in the resistance groups cannot be solely attributed to host gene expression, implying that targeting pathways involving host genes might not be the most effective approach. Rather than concentrating on pathways involving host genes, our results suggest that understanding the mechanisms of action of snoRNAs could provide promising avenues for developing novel therapeutic targets to enhance drug response in pediatric ALL.

In France, lomustine was added to 7+3 in patients >60 years. The most frequent second-line therapy in the whole IC population was salvage chemotherapy with high-dose or intermediate-dose cytarabine or a combination of either of these with anthracycline (daunorubicin, idarubicin, or amsacrine) in France and decitabine or the combination of cytarabine, etoposide and mitoxantrone in the USA. Azacitidine/venetoclax combination was used in second and third line in France and USA and it was the most frequent third-line therapy (35.8%) in France. Patients received IC in combination with targeted therapies (mainly midostaurin) in 18% of the IC population in France and 12.4% of the IC population in the USA...In the REAL-IDH study we observed that treatment patterns in mIDH1 or wild type patients were similar. More specific data is needed regarding the sequencing of treatment regimens and overall outcomes in mIDH1 AML patients.

Altogether, the results of this study suggest that amsacrine triggers apoptosis in K562 cells by inhibiting BCL2L1 expression through the SIDT2/NOX4/ERK-mediated downregulation of HuR. Furthermore, a similar pathway also explains the cytotoxicity of amsacrine in CML MEG-01 and KU812 cells.

P1/2, N=38, Recruiting, Heinrich-Heine University, Duesseldorf | Not yet recruiting --> Recruiting

P1/2, N=38, Not yet recruiting, Heinrich-Heine University, Duesseldorf

In this study, we screened an in-house small-molecule library targeting LSD1, an FDA-approved drug amsacrine for acute leukemia and malignant lymphomas was found to exhibit moderate anti-LSD1 inhibitory activity (IC = 0.88 μM)...Moreover, tumor growth was also suppressed by compound 6x in mice. Altogether, our findings demonstrated that acridine-based novel LSD1 inhibitor 6x may be a lead compound for the development of activating T cell immune response in gastric cancer cells.

Current sequential conditioning regimens combine intensive AML-like induction therapy with TBI or alkylators like Busulfan, Treosulfan and Melphalan. The first and currently widely accepted prototype of this treatment strategy is the Fludarabine/Amsacrine/Ara-C (FLAMSA) protocol, which has been modified multiple times by changing parts or adding additional cytotoxic drugs to further improve clinical results...ATG was used in 29 (70.7%), post-transplant cyclophosphamide in 8 patients (19.5%) in addition to GvHD prophylaxis with a calcineurin inhibitor and MMF... The combination of sequential FLAMSA+Alkylator with Venetoclax appears to be safe and highly effective without increasing the rate of non-hematologic toxicity. This may be a smart way to extend the limited therapy options of patients with high-risk myeloid malignancies. To further validate these insights and enhance the idea of smart conditioning, a controlled prospective clinical trial should be the next step.