Treatment of MM cells with the selective AURKA inhibitor LY3295668 induced dose-dependent cytotoxicity, caspase-3/7 activation, and cellular senescence. These findings underscore AURKA expression as a prognostic marker in plasma cell disorders and support the therapeutic potential of combining AURKA inhibition with selinexor for bortezomib-resistant MM and PCL. To explore biomarker-driven strategies for optimizing therapeutic outcomes, future studies are warranted.

Serial assessments were performed before and during treatment with bortezomib and dexamethasone for MM, and later with daunorubicin/cytarabine for AML. It demonstrates the earliest events in pDC-AML evolution. Furthermore, the immature immunophenotype raises the question of appropriate treatment, since a diagnosis of acute undifferentiated leukemia can be established.

Acquired drug resistance is a major cause of poor prognosis in multiple myeloma (MM). Treatment with the SLC19A1 inhibitor sulfasalazine or the STING inhibitor H-151 reduced mtDNA release and restored BTZ sensitivity. These findings highlight SLC19A1 and STING signaling as potential therapeutic targets for overcoming acquired drug resistance in MM.

Lenalidomide, bortezomib, and dexamethasone, demonstrate significant clinical efficacy in treating multiple myeloma.

Mechanistic studies revealed that E46K/DOPAC aggregates were preferentially degraded via the ubiquitin-proteasome system (UPS), as proteasome inhibition with MG132 enhanced toxicity and intracellular accumulation. In contrast, autophagy inhibition by chloroquine paradoxically reduced toxicity, indicating redirection toward UPS-mediated degradation...Overall, our results demonstrate that DOPAC reshapes the biophysical and toxicological properties of Syn aggregates, especially E46K species, by promoting less harmful oligomers and enhancing proteostatic clearance. These findings highlight DOPAC as a promising modulator of Syn aggregation and pathology.

P2, N=46, Completed, Dana-Farber Cancer Institute | Active, not recruiting --> Completed

This study is the first to demonstrate that afatinib inhibits ESCC cell growth in vivo and in vitro by inducing ferroptosis, and that the regulatory axis Nrf2/xCT/GPX4 is involved in this process. The results of this study provide a novel mechanism for afatinib mediated anti-ESCC activity.

The downregulation of HIF-1α expression in 2-ANPC-treated cancer cells was due to enhanced proteasome-mediated degradation, whereas the proteasome inhibitor MG-132 effectively reversed this downregulation...Lastly, using various computational tools, we identified four potential binding sites for 2-ANPC to interact with HIF-1α, HIF-1β, and the p300 complex. Collectively, we show here, for the first time, that HIF-1α is a novel molecular target for the 2-aminopyrrole derivative (2-ANPC), thereby illustrating it as a potential scaffold for the development of potent chemotherapeutic agents with anti-angiogenic activity.

P1, N=24, Recruiting, National Cancer Institute (NCI) | Suspended --> Recruiting

P=N/A, N=72, Active, not recruiting, Takeda | Recruiting --> Active, not recruiting

P2, N=30, Completed, Fred Hutchinson Cancer Center | Active, not recruiting --> Completed

The regulatory mechanism of PPG on Nrf2 was further investigated using cycloheximide(CHX) to inhibit de novo protein synthesis, the proteasome inhibitor MG132 to block proteasomal degradation, and co-immunoprecipitation to assess Nrf2 ubiquitination...In vivo, PPG significantly suppressed tumor growth and reduced the expression of Ki67, GPX4, and Nrf2 in xenograft tumors compared with the control group. PPG induces ferroptosis in bladder cancer cells by promoting Nrf2 ubiquitination and proteasomal degradation, thereby inhibiting tumor cell growth.