DUSP6 (Dual specificity phosphatase 6)

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.

DUSP5 silencing-induced growth suppression was partially due to G1 cell cycle arrest, associated with p21 upregulation. Collectively, our findings highlight DUSP5 as a potential therapeutic target for lung cancer.

Notably, the anti-malignant effects of DUSP6 knockdown were partially reversed by the mitophagy inhibitor cyclosporin A. Mechanistically, DUSP6 modulates mitophagy by increasing the phosphorylation status of mTOR, a central autophagy regulator, and DUSP6 knockdown-induced mitophagy was partially restored after treatment with mTOR activator MHY1485. Our findings indicate that high DUSP6 expression promotes BC progression by inhibiting mTOR-mediated mitophagy, leading to a poor prognosis for BC patients. These insights suggest DUSP6 as a potential therapeutic target in the treatment of BC.

P1, N=227, Terminated, Novartis Pharmaceuticals | Active, not recruiting --> Terminated; Business reasons and not due to any safety concerns

Together, these findings uncover a novel KBD-targeting mechanism of MKP3 inhibition by BCI and highlight the potential of selectively modulating MAPK phosphatases through allosteric disruption of kinase-phosphatase interactions. This strategy may offer a new avenue for the design and optimization of targeted phosphatase inhibitors.

Our group has developed a cancer-specific drug conjugate (ACXT-3102), consisting of a proapoptotic sigma-2 ligand as a delivery moiety (SV119), linked to an inhibitor of the cystine antiporter xCT (dm-erastin), an established inducer of ferroptosis. We suspected that this was a compensatory reaction and that ACXT-3102-induced cancer cell death would be augmented by inhibition of MAPK/ERK signaling. We successfully combined ACXT-3102 with trametinib (MEK inhibitor) to enhance the overall efficacy of treatment in vitro and in vivo, presumably by targeting ACXT-3102-induced upregulation of MAPK/ERK.

P1, N=227, Active, not recruiting, Novartis Pharmaceuticals | Trial primary completion date: Nov 2025 --> Jul 2025 | Trial completion date: Nov 2025 --> Jul 2025

Our group has developed a cancer-specific drug conjugate (ACXT-3102), consisting of a pro-apoptotic sigma-2 ligand as a delivery moiety (SV119), linked to an inhibitor of the cystine antiporter xCT (dm-Erastin), an established inducer of ferroptosis. We suspected this was a compensatory reaction and that ACXT-3102-induced cancer cell death would be augmented by inhibition of MAPK/ERK signaling. We successfully combined ACXT-3102 with trametinib (MEK inhibitor) to enhance the overall efficacy of treatment in vitro and in vivo, presumably by targeting ACXT-3102-induced upregulation of MAPK/ERK.

In vivo experiments further demonstrated that PP1A knockdown significantly enhances the efficacy of Lenvatinib-ICIs combination therapy. Overall, our findings highlight PP1A as a critical regulator of ferroptosis and antitumor immunity, suggesting its potential as a predictive biomarker and therapeutic target for improving outcomes in advanced HCC.