In therapy-sensitive wild-type ER cells with low basal PML1 levels and PI3K/MAPK activity, fulvestrant's ER-suppressive effects overcome drug-induced elevated PML1 and PI3K/MAPK activity, thereby maintaining therapeutic efficacy...Notably, reducing PML1 levels through knockdown or arsenic trioxide (ATO), an FDA-approved PML1 degrader, disrupts this resistance circuit and restores endocrine sensitivity. Treatment of ATO resensitizes ER Y537S-bearing resistant tumors to endocrine therapy in xenograft models. These findings establish PML1 as a central hub of resistance, linking ER signaling to the activation of the PI3K/MAPK survival pathway.

P2/3, N=345, Active, not recruiting, Pharma Mar S.A. | Recruiting --> Active, not recruiting

Dendritic SiO2 nanoparticles were sequentially loaded with elesclomol-copper complex (ESCu) and hemin, followed by hyaluronic acid (HA) coating to achieve CD44-mediated tumor targeting and HAase/pH-responsive drug release...In vivo results further demonstrated enhanced tumor accumulation, superior tumor growth inhibition, and favorable preliminary biosafety. This work provides a targeted nanotherapeutic strategy for enhanced cancer treatment through cuproptosis-photothermal combination therapy.

These results indicate that ATO suppresses the malignant phenotype of A549 cells by inhibiting mTOR phosphorylation, downregulating key BER components, and activating the extrinsic and intrinsic apoptotic pathways, providing experimental evidence for further studies of ATO in lung adenocarcinoma therapy.

P1, N=5, Terminated, Genprex, Inc. | Phase classification: P1/2 --> P1

P1/2, N=62, Recruiting, Genprex, Inc. | Trial primary completion date: Feb 2026 --> Jun 2026

Therefore, this platform is particularly suited for the treatment of FLT3-ITD AML while potentially applicable to other AML subtypes with high CD71 expression. By enabling specific intracellular accumulation of HHT and multitarget inhibition of FLT3 signaling pathways, this system achieves enhanced anti-AML efficacy both in vitro and in vivo, offering strong potential for future clinical translation.

Notably, combining the SIRT5 inhibitor MC3482 with the cuproptosis inducer Elesclomol-Cu synergistically suppresses tumor growth in vivo, suggesting a promising therapeutic strategy. These findings elucidate mechanisms underlying cuproptosis resistance and propose a novel treatment approach for LUAD.

From approval of immune checkpoint inhibitors and lurbinectedin, a newer chemotherapy agent, to novel immunotherapies such as tarlatamab, a DLL3-CD3 bispecific T-cell engager, and other upcoming promising drugs, the therapeutic armamentarium for SCLC is steadily expanding. In this study, we review the current landscape of both systemic therapy as well as radiation therapy for SCLC, with a focus on major developments over the past decade, current standards of care, and novel therapeutics that are expected to revolutionize the treatment of this aggressive malignancy.

Elesclomol (15 nM) and copper chloride (CuCl₂, 10 µM) were used to induce cuproptosis, while DLAT overexpression and S6 kinase inhibition were used to clarify signaling processes. MELK expression was considerably elevated in DLBCL tissues and cell lines (P < 0.05)...On the other hand, MELK-mediated effects on cuproptosis and intracellular copper buildup were abolished by S6K suppression or DLAT overexpression. Through the PI3K/mTOR/S6K-DLAT axis, MELK imparts resistance to cuproptosis and increases DLBCL cell survival. MELK targeting may increase copper-induced cytotoxicity, offering a possible DLBCL treatment approach.

The resulting nanoparticles were investigated in a refractory AML mouse model (AML1-ETO & C-KITD816V) with a high level of CXCR4 and in the t(8; 21)-positive AML cell line Kasumi-1. It was shown that E5-LNP@siAE effectively achieved RNAi of AML1-ETO and antagonism of CXCR4, thereby synergistically inducing effective multi-lineage differentiation, leading to significantly enhanced differentiation-post apoptotic responses of AML cells to homoharringtonine and remarkably prolonged survival in refractory AML mice.

Dynamic changes in serum VEGF levels were associated with treatment response; however, these findings should be interpreted with caution due to the retrospective design and absence of a control group. Further well-designed prospective controlled studies are warranted to validate these observations.