bortezomib

P1/2, N=300, Active, not recruiting, Australasian Leukaemia & Lymphoma Group | Recruiting --> Active, not recruiting

Functionally, MAGEC2 promoted malignant proliferation and induced resistance to adriamycin and bortezomib. MAGEC2 overexpression also exacerbated bone lesions in vivo. Collectively, these findings identify MAGEC2 as both a prognostic biomarker and a promising therapeutic target in MM, and highlight its role as a multifunctional regulator of the ubiquitin system.

Here we show calcium/calmodulin-dependent protein kinase II gamma (CaMKII-γ) regulates bortezomib-resistant MM (BRMM) via AMPK-ULK1-autophagy axis. High-throughput screening identified ruxolitinib as a selective CaMKII-γ inhibitor, which reverses BRMM resistance in vitro (using U266 and KMS11 bortezomib-resistant cell lines) and in vivo (using female BALB/c nude mouse model), with efficacy comparable to genetic CaMKII-γ ablation, providing a potential therapeutic strategy for BRMM with broader implications to improve patient outcomes in the future.

CDKN3 overexpression prevented the effects of si-MYBL2 on ferroptosis and BTZ sensitivity in MM cells by interacting with the PI3K/Akt signaling pathway. In conclusion, knockdown of MYBL2 promoted ferroptosis and enhanced the BTZ sensitivity of MM cells through transcriptional regulation of CDKN3 and inactivation of the PI3K/Akt signaling pathway.

P3, N=480, Recruiting, PETHEMA Foundation | Not yet recruiting --> Recruiting

P3, N=1000, Not yet recruiting, Janssen Research & Development, LLC

This is the first study to model gastrointestinal side effects of bortezomib in rodents, implicating neuroimmune dysregulation of the vagus nerve. Our data show that the gut microbiota is not a primary driver of bortezomib side effects. However, the absence of a symptom profile in FMT mice suggests that, in GF mice, the gut microbiota beneficially modulates the host to protect against bortezomib side effects. Further studies are required to determine whether this can be harnessed to mitigate clinical complications of bortezomib.

P2, N=160, Not yet recruiting, Massachusetts General Hospital | Initiation date: Apr 2026 --> Aug 2026

This study uncovers a glucocorticoid-sensitive inhibitory axis wherein GR-PPP1CB constitutively suppresses STING-TBK1-IRF3 signaling in MM. DXM relieves this suppression, reactivating innate anti-tumor immunity. PP1 inhibition represents a promising therapeutic strategy to enhance anti-myeloma immunity and overcome immune evasion.

P=N/A, N=333, Recruiting, Shanghai Zhongshan Hospital

P3, N=419, Active, not recruiting, Janssen Research & Development, LLC | Trial completion date: Apr 2029 --> Mar 2027

P3, N=386, Completed, Celgene | Active, not recruiting --> Completed | Trial completion date: Apr 2027 --> Apr 2026 | Trial primary completion date: Apr 2027 --> Apr 2026