DUSP6 (Dual specificity phosphatase 6)

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.

We constructed a RiskScore model for predicting the survival outcomes based on fibroblasts-related genes. These findings highlighted the role of fibroblasts in GBM development and offered six potential therapeutic targets (VWA1, DUSP6, LOXL1, IGFBP4, CYGB, and ZIC3) for GBM treatment. Additionally, immune infiltration analysis and drug sensitivity prediction further supported the model's utility in guiding personalized treatment of GBM.

In conclusion, our findings highlight the importance of the OCT4-DUSP6 pathway in NSCLC progression. Furthermore, the OCT4-DUSP6 axis is a potential therapeutic target for NSCLC.

Our findings confirm AZD4625 as a highly active KRASG12C inhibitor. This data also supports the use of PDX models in understanding resistance mechanisms that may be leveraged to develop more active combination therapies.

These findings reveal that DUSP6 independently regulates migration and metabolism in PDAC, emphasizing its dual role in disease progression. This study underscores the significance of DUSP6 as a potential therapeutic target and provides new insights into its contributions to PDAC progression.