TAFAZZIN (Tafazzin)

Co-targeting SOX9 and YAP1 offers a promising and safe broad-spectrum preventive/therapeutic approach for iCCA, potentially overcoming resistance to YAP1 inhibition. The adaptive resistance mechanism identified may extend to other malignancies, providing insights for addressing the advanced resistant to YAP1-TEAD-directed therapies.

Patients with high expression of HSPA5, YAP, and TAZ exhibited significantly poorer overall survival. Collectively, our findings suggested that HSPA5 promotes PMT through the stabilization of YAP/TAZ and identified HSPA5 as a promising therapeutic target for GBM patients.

TAZ modulates gluconeogenesis and accelerates tumor growth, whereas its knockdown attenuates tumor progression. TAZ interacts with GR, suppressing its transcriptional activity on gluconeogenic gene promoters.

RNA-seq, and spatial transcriptomics and proteomics of Yap/Taz knockout skin revealed substantial downregulation of matrisome genes, including type I ( Col1a1, Col1a2) and type III ( Col1a3 ) collagens, which together constitute more than 90% of the skin's collagen content. These findings demonstrate that Yap/Taz are essential for dermal ECM homeostasis, highlighting their therapeutic potential in skin regeneration, fibrosis, and aging-related ECM decline.

However, adjuvant chemotherapy significantly led to better overall survival. The Hippo pathway is frequently deregulated (nuclear YAP/TAZ in 61.4% of patients), suggesting it is a compelling novel therapeutic target for this aggressive disease.

We find that lineage transition is accompanied by a redistribution of FOXA1 and TEAD cistromes from PRAD to NEPC-specific enhancers and requires the pioneering activity of FOXA1. Thus, extracellular matrix/integrin signaling in the PRAD tumor microenvironment restrains NE lineage plasticity, highlighting a potential path for pharmacological inhibitors in modulating treatment-induced lineage change.

Furthermore TAC level was considerably lower in bladder cancer patients (p < 0.01), while the TOS level was significantly higher compared to the control group(p < 0.05). Finally, our findings suggested that NRF2 and TAZ, as transcriptional factors, are associated with higher grades of bladder cancer as well as oxidative stress in patients with bladder cancer.

Moreover, analysis of The Cancer Genome Atlas (TCGA) datasets showed elevated CDC6 expression across multiple human tumors with high YAP and TAZ activity, and a strong positive correlation between CDC6 and YAP/TAZ expression. These findings highlight that the conserved YAP/TAZ-CDC6 axes are key drivers of malignant transformation and underscore their potential as therapeutic targets across diverse cancer types.

Dual inhibition of YAP1 and TAZ was required to maximally suppress YAP1/TAZ expression and reduce their nuclear accumulation, transactivation of TEAD, and activation of downstream genes. Conclusions These findings show that combined YAP1 and TAZ inhibition holds promise for the treatment of GCPMs, a highly lethal disease with an urgent need for novel treatment options.

Finally, belinostat extended in vivo survival only in IDHmut glioma models, not in IDHmut GBM models. Our findings provide a mechanistic rationale for further studies of HDACi in IDHmut glioma patients, as well as the potential use of YAP/TAZ as a biomarker of HDACi sensitivity in cancers.

Simultaneous loss of Brg1 and Pten in pancreatic ductal cells results in ITPN formation via the activation of the YAP/TAZ pathway in the mouse model. The YAP/TAZ pathway is a key driver of ITPN formation and is a potential therapeutic target for ITPN and ITPN-derived PDAC.

Importantly, both compounds displayed the same efficacy in 2D and 3D culture models, and a single treatment with entinostat improved survival in an immunocompetent mouse model compared with fluvastatin and standard cisplatin-pemetrexed chemotherapy, which showed similar anti-tumor effects. Combination of entinostat with anti-PD1 even eradicated tumors in several mice and immunized them against re-transplantation of tumor cells. Overall, the drug sensitivity data provided by this study represents a resource to facilitate future clinical investigations to improve treatment of PM.