TAF1 (TATA-Box Binding Protein Associated Factor 1)

Drug sensitivity screening identified six small molecules (PD0325901, ERK-6604, paclitaxel, ribociclib, TAF1, and lapatinib) that targeted SLC12A5-related pathways. Crucially, multivariate Cox regression analysis confirmed that SLC12A5 was an independent prognostic factor (HR p = 0.04). This study established SLC12A5 as a novel biomarker for GBM, uniquely bridging molecular dysregulation, edema pathogenesis, and radiomics with implications for prognosis and targeted therapy.

LINC01940 is a cancer-testis lncRNA that promotes GC progression and cisplatin resistance by enhancing ribosome biogenesis via the METTL16/IGF2BP3-TAF15-NOL11 axis. These findings suggest its potential as a prognostic biomarker and therapeutic target in GC.

Moreover, the concomitant upregulation of TAF1 and KCTD9 Kbhb serves as a poor prognostic factor for metastatic CRC patients. Taken together, our findings bridge the newly identified Kbhb modification dependent regulatory mechanism that modulates the anticancer function of KCTD9, and provided insight into potential strategies for targeting epigenetic factor and combating the KCTD9 inactive-driven CRC metastasis.

Consistent with these findings, postmortem brain tissue from XDP patients revealed similar myelin pathology, including near-complete loss of myelin in parts of the medial prefrontal cortex. Together, these results identify oligodendrocyte dysfunction and myelin loss as previously unrecognized contributors to XDP pathogenesis, providing new mechanistic insight into this debilitating disorder.

Our work shows, for the first time, a broad overview on the extra-telomeric role of TRF2 in human cancer, further revealing a new axis through which TRF2 contributes to cancer progression.

This is the first systematic study addressing the concept of thymus-like phenotype in benign lymphoepithelial salivary gland tumors, showing that the majority of NSLAs (65%) belong to this poorly characterized category. Frequent CYLD mutations in these histologically distinct tumors represent a novel addition to the spectrum of CYLD-mutated salivary neoplasms.

Our results highlight the potential utility of Cisd2 and its activator hesperetin in chemotherapy involving doxorubicin.

However, these findings derive solely from publicly available datasets and lack experimental validation, which may introduce bias. Single-cell analyses cover only a few tumor types, drug-gene relationships remain correlative, and the absence of longitudinal clinical data prevents evaluation of true prognostic value.

Additionally, this study uncovers a small molecule FBXO5 stabilizer that disrupts the β-TrCP1-FBXO5 interaction, thereby markedly enhancing NSP7 degradation and effectively mitigating SARS-CoV-2 infection. Taken together, the findings reveal a novel mechanism for NSP7 regulation and suggest that small-molecule activators of the E3 ubiquitin ligase FBXO5 represent a promising new class of host-directed antiviral therapies.

We applied a structure-guided approach to generate cereblon recruiting Proteolysis Targeting Chimera (PROTAC) degraders of TAF1 using the chemical scaffolds of ceralasertib and GNE371...The results showed that inhibition of the bromodomain is not sufficient to inactivate TAF1 functions, whereas a PROTAC approach induces strong biological effects. Furthermore, TAF1 PROTACs have therapeutic potential against AML and other sensitive tumors.

This pilot study highlights the potential role of NGS analysis on solid biopsy in the assessment of the mutational profile of lung NET. A comparison of germline and somatic mutations is critical to identifying putative tumor driver mutations. In perspective, the enrichment of a subpopulation of cancer cells in the blood, with one or more specific mutations, is information of enormous clinical relevance, either for prognosis or therapeutic decisions. Translational studies on large prospective series are required to establish the role of liquid biopsy in lung NET.

However, reference compounds and in vitro cell viability and cytotoxicity assays in cancer cell lines demonstrated superior effects of high affinity tyrosine kinase inhibition compared to inhibition of the TAF1 bromodomain. Our results highlight the feasibility of dual tyrosine kinase-bromodomain targeting to overcome disease mechanisms while also revealing the increased efficacy of FLT3-targeted compounds in AML.