This indicates that although proteasomal inhibition is not inflammatory, TNF present in the microvascular environment synergizes with the drugs to compromise endothelial function. Our observations provide an explanation for how microvascular damage potentially underlies tissue injury driven by Bortezomib or Carfilzomib.

P2, N=20, Active, not recruiting, Institute of Hematology & Blood Diseases Hospital, China | Recruiting --> Active, not recruiting | Trial completion date: Apr 2027 --> Apr 2028 | Trial primary completion date: Oct 2025 --> Apr 2026

P2, N=28, Recruiting, Fondazione Italiana Linfomi - ETS | Trial primary completion date: Jan 2026 --> Jul 2027

P=N/A, N=22, Completed, The First Affiliated Hospital of Zhejiang Chinese Medical University

As a TSC2 inhibitor, AcTor should not be used alone in cancer. When combined with proteasome inhibitors, the pharmacodynamics of AcTor shifts towards the development of a mitochondrial catastrophe in AML, which is durable, broad range, agnostic to TP53 mutations and to the acquisition of resistance to common clinical anti-AML drugs.

P3, N=1645, Completed, National Cancer Institute (NCI) | Active, not recruiting --> Completed | Trial completion date: Sep 2027 --> Mar 2026

Biodistribution studies in Ehrlich tumor-bearing mice showed significant tumor uptake (6.8 %ID/g at 2 h p.i.) with rapid clearance from blood and normal tissues. These findings highlight the potential of 177Lu-AAZTA5-Carfilzomib as a promising proteasome-targeted theranostic candidate for multiple myeloma.

OGM revealed multiple clinically relevant structural variants and partner genes impacted in adult T-lymphoblastic leukemia that were not part of the standard cytogenetic workup, thereby improving genomic characterization and risk assessment. Identification of alterations involving FBXW7, NOTCH1, TLX3::BCL11B, PHF6, MYB, and CDKN2A provided a comprehensive genomic profile that informed counseling regarding prognosis and supported treatment selection. Integrating OGM into routine evaluation of myeloid and lymphoid neoplasms has the potential to streamline diagnostic workflows and ensure that disease-defining aberrations critical for diagnosis, prognosis, and targeted therapy selection are not overlooked.

These preclinical findings support CD44 overexpression as a marker associated with inferior survival in MM and provide a rationale for pharmacologic tumor priming with ATRA and bortezomib to enhance NK cell-mediated cytotoxicity. However, the therapeutic strategy requires further validation in heterogeneous patient-derived models and prospective clinical studies before clinical efficacy can be inferred.

Low expression of peripheral blood CD3⁺CD56⁺CD161⁺ NKT cells is associated with increased tumor burden and bortezomib resistance in NDMM, suggesting its potential as a predictive biomarker for treatment response.

The addition of bortezomib or daratumumab might improve outcomes. B-cell maturation antigen-targeted therapies have shown early efficacy. The participation of patients with PBL in prospective clinical trials is warranted.

P2, N=15, Terminated, University of Southern California | Completed --> Terminated; Sponsor stopped study early.