MTOR mutation

Here, we report a reliable and efficient methodology for the expression and purification of highly active p70S6K1 (His-actS6K1) in quantity and quality that is suitable for biochemical/biophysical studies and high-throughput enzymatic assays. Our developed methodology offers a rapid and cost-effective approach for producing constitutively active His-actS6K1, which can be utilized in academic research and biotechnology.

One of two patients treated with dabrafenib and trametinib showed a copy number gain in post-treatment tissue NGS, potentially indicating resistance. Liquid biopsy provides valuable supplementary information when tissue samples are insufficient. Further studies are necessary to understand resistance mechanisms and develop strategies to overcome them in BRAF-targeted therapy.

We present a frontal lobe intra-axial parenchymal schwannoma containing a CHD7::VGLL3 gene fusion presenting in a 19 month-old male, the youngest patient yet reported for this lesion.

The present study aimed to investigate the efficacy of the CDK4/6 inhibitors (CDKi) palbociclib and ribociclib, and the PI3K/Akt/mTOR pathway inhibitors (PI3Ki) gedatolisib, buparlisib and alpelisib, in suppressing cell viability of HPV‑positive and ‑negative HNSCC cell lines. Whereas PI3Ki induced apoptosis and attenuated cellular metabolism, CDKi led to cell cycle arrest. Further research should be performed to elucidate whether (a combination of) these inhibitors may be effective therapeutic agents for patients with HNSCC.

Although it is known that hyperactivation of the mechanistic target of rapamycin complex 1 (mTORC1) due to TSC2 gene mutations contributes to aberrant cell growth in LAM lung, tumor origin and invasive mechanism remain unclear...Fludarabine, a potent STAT1 inhibitor, induced the death of TSC2- deficient cells, increased caspase-3 cleavage, and phosphorylation of necroptosis marker RIP1...Interestingly, IFN-γ treatment increased STAT1 phosphorylation and PD-L1 expression, indicating that STAT1 aids TSC2-deficient tumor cells in evading immune surveillance in LAM. Our findings indicate that STAT1 signaling is critical for LAM cell survival and could be targeted to treat LAM and other mTORC1 hyperactive tumors.

The study reveals that over expression of CD163 and α-SMA is strongly associated with disease outcome. The combinations of all the four marker expression profile will be emerging strategy towards prognosis and also to determine survival outcomes in patients. This is a pioneering observation of these combinations of markers in OSCC despite certain limitations.

Asp167 has few effects on both the catalytic function activity of PIM-1 and PI3K/AKT/mTOR pathway, even though the binding ability of PIM-1 protein to its substrate is dramatically inhibited by D167A mutation. Altogether, the mutant probes works well as visualization tools to unearth the function of active sites in PIM-1 kinase, not only facilitating the further clarification of molecular mechanism underlying PIM-1 related signaling pathways, but also shedding light on drug development and disease therapy targeting PIM-1 protein.

The ChemoResist signature could precisely predict survival in PDAC undergoing resection and chemotherapy, and its predictive value surpassed TNM stage and other clinicopathologic factors. Moreover, the ChemoResist classifier could assist with identifying patients who would more likely benefit from adjuvant chemotherapy.

It is used for the treatment of adult patients with hormone receptor-positive, human epidermal growth factor receptor 2 negative metastatic breast cancer with at least one alteration on PIK3CA/AKT1/PTEN. In this short perspective, Capivasertib's physicochemical properties, synthesis, mechanism of action, binding mode, pharmacokinetics, drug interaction studies, and treatment-emergent adverse events are discussed.

Moreover, the role of PIK3CA mutations in vascular overgrowth syndromes is explored, alongside emerging targeted therapies, such as PI3K and MEK inhibitors, that promise improved outcomes for patients with these challenging conditions. The integration of histology, molecular diagnostics, and multidisciplinary care remains critical for the accurate diagnosis and optimal treatment of vascular anomalies in the era of precision medicine.

Renal malignant eAML also known as malignant PEComa of the kidney is an exceedingly rare tumor with propensity for malignant behavior that frequently displays a variety of germline mutations as well as GA indicative of potential efficacy of MTOR pathway inhibitors.

Overall, 73% (8/11) tumors with TSC2 IHC loss and underlying pathogenic alterations in TSC2 showed heterogeneous protein loss, with rare interspersed positively staining tumor cells. These data support TSC2 IHC as a potentially useful assay for the diagnostic workup of renal tumors suspected to belong to the TSC/mTOR-associated subgroups.