DUSP6 (Dual specificity phosphatase 6)

However, these predictions require confirmation through relevant in vitro and in vivo experimental studies to verify the precise mechanism, which is a limitation of the present work and a future scope. The online version contains supplementary material available at 10.1007/s40203-026-00604-9.

Here, we revealed that AP-1-mediated activation was attenuated in CAR T cells impaired by tumor CD58 loss, driving a decrease in mitochondrial biogenesis, metabolic kinetic impairment, mitochondrial membrane potential loss and ROS accumulation...Our findings repositioned CD58 not merely as an immune synapse component but also a metabolic checkpoint in CAR T-cell biology, the loss of which triggers AP-1-dependent mitochondrial derangement and creates a permissive landscape for intrinsic apoptosis, which can be ameliorated by ablation of the inhibitory phosphatase DUSP6. Crucially, DUSP6 ablation represents a promising engineering target to potentiate CAR T-cell efficacy in broader applications.

In vivo experiments demonstrate that sh-DUSP6 suppresses thyroid cancer tumor growth in mouse models. DUSP6 promotes the metastasis of thyroid cancer by facilitating the formation of neutrophil extracellular traps via IL-8.

P2, N=13, Terminated, Dana-Farber Cancer Institute | Active, not recruiting --> Terminated; This was a Simon two stage design trial that terminated after the first stage due to lack of response.

This case underscores the importance of molecular diagnostics in identifying rare genetic alterations and highlights the need for further research into targeted therapies for BRAF fusion-driven cancers. The discovery of this novel fusion expands our understanding of the molecular landscape of PTC and provides a foundation for future therapeutic development.

Furthermore, pan-cancer analyses implicate the BRAF25 signature in poor prognosis across diverse BRAF-driven malignancies. In conclusion, stratifying patients by transcriptional BRAF oncogenic activity, instead of relying solely on BRAF mutation status, provides a more precise approach to guide clinical decision-making and improve therapeutic outcomes.

This research identifies a key mechanism of SAMHD1-driven immunosuppression and highlights its important role in oncolytic adenovirus therapy. This study provides a theoretical basis for targeting SAMHD1 as a drug therapy strategy in patients with NSCLC.

Here we demonstrate that the HMG-CoA reductase inhibitors atorvastatin and rosuvastatin modulate inflammatory survival pathways in colorectal cancer cells in a manner consistent with targeted interference with the protease-activated receptor 2 (PAR-2)-extracellular signal-regulated kinase (ERK)-tumour necrosis factor-α (TNF-α) signalling axis. Collectively, these data indicate that clinically deployed statins target the PAR-2-ERK axis and are associated with re-activation of apoptotic pathways in inflammatory colorectal cancer models, while leaving open the possibility that additional statin-responsive networks contribute to their pro-apoptotic effects. This mechanistic framework provides biological plausibility for epidemiologic observations linking statin use with reduced colorectal cancer risk and improved outcomes, and supports further translational evaluation of PAR-2-directed statin strategies in colorectal malignancy.

Additionally, other regulating proteins, like the transcription factor Ets2 and the p53, which were regulated by hypoxia and acidosis as well, correlated strongly with Dusp6 expression. It can be concluded that ERK1/2 activation during acidosis and/or hypoxia results from Dusp6 repression, which could be induced by mTor signaling or the expression of other regulating proteins.

RNA sequencing identified early growth response protein 1 (EGR1), fos proto-oncogene (FOS), and dual-specificity phosphatase 6 (DUSP6) as candidate biomarkers of treatment response. Selumetinib, identified by computational drug screening, demonstrates efficacy against RDEB-SCCs in vitro and in vivo, suggesting its potential for clinical use.

Here, we demonstrate that the second-generation XPO1 inhibitor Eltanexor synergizes with MRTX1133 to enhance its efficacy in multiple PDAC models. By enhancing KRASG12D inhibitor activity and potentially reducing the required therapeutic dose, this combination approach offers a novel means to delay or overcome resistance. These findings provide a strong preclinical rationale for clinical trials evaluating KRAS inhibitors in combination with XPO1 inhibitors and may significantly improve outcomes for a substantial subset of PDAC patients who currently lack effective targeted treatment options.