PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)

Notably, we observed racial disparities in expression patterns, with African American patients exhibiting more pronounced downregulation of p85α and upregulation of p55α than European Americans, potentially contributing to differential clinical outcomes. This is the first study to systematically evaluate p85α and p55α expression across diverse cancers and populations, highlighting the role of alternative splicing in PI3K pathway dysregulation and its relevance to cancer progression and health disparities.

Using this tool to mimic the mutation-specific dynamics in MCF10A mammary epithelial cells, we found that PI3K signaling patterns alone were sufficient to reproduce key features of the PIK3CA H1047R-associated EMT phenotype but not the ErbB2-associated proliferative phenotype. These findings suggest that the temporal encoding of pathway activity, not merely its magnitude, can drive some phenotypic changes in oncogenic progression, explain how distinct mutations within a common signaling pathway can produce divergent cellular phenotypes, and provide a workflow for interrogating the functional consequences of changes in signaling dynamics.

Additionally, molecular docking is used to predict direct binding between CaA and the PI3K p110α subunit (PIK3CA). Together, these procedures provide a reproducible framework to examine ferroptosis mechanisms and the therapeutic efficacy of natural compounds in glioma research.

Treatment with the PI3Kα-selective inhibitor alpelisib suppressed lesion formation and reversed pro-angiogenic signaling in both mouse models and patient-derived cerebral cavernous malformations organoids. These findings uncover a convergent mechanism involving MAPK and PI3K pathway activation in cerebral cavernous malformations pathogenesis and demonstrate that PI3Kα inhibition may offer a viable therapeutic strategy for a disease that currently lacks effective pharmacological treatment.

Taken together, our study reflected the impact of the HER2 status on the clinicopathological and molecular features of TNBCs, which might offer additional introspection and improvement for translational studies and therapeutic decisions for TNBCs.

HER2-high and HER2-low/TNBC breast cancers demonstrate distinct clinicopathologic and molecular profiles. Therapy-associated enrichment of PIK3CA mutations and their association with aggressive behavior underscore their prognostic and therapeutic significance in HER2-positive disease. Further studies are needed to clarify their role in guiding personalized treatment strategies.

Our data support the clinical implementation of a tailored, histology-driven MP algorithm, potentially optimizing the genomic testing resources in SGCs.

BZD exerts anti-LC effects through multi-target regulation, particularly involving AKT1, PIK3CA, SRC, and HSP90AA1, as well as suppression of the PI3K-AKT signaling pathway. These findings provide a mechanistic basis for its potential clinical application in LC therapy and warrant further in vivo investigation.

In the CAPItello-291 trial, capivasertib and fulvestrant demonstrated efficacy in patients with up to two prior lines endocrine therapy, but its use in late-line settings has not yet been reported. In this article, we report a case of a woman with metastatic recurrent breast cancer who was treated with capivasertib and fulvestrant was used as the late-line treatment, resulting in a progression-free survival of 8 months.

P=N/A, N=500, Not yet recruiting, Hoffmann-La Roche

Furthermore, CYH33 possessed potent activity against the growth of LUSC with hyperactivated PI3K signaling. Collectively, the dual-targeting of CYH33 that directly blocked PI3Kα in tumor cells and disrupted CAF-mediated pro-metastatic signaling supported PI3Kα inhibitors as a potential therapeutic approach for advanced LUSC.

In vitro cytotoxicity assays were then performed in MCF-7 and MDA-MB-231 breast cancer cell lines, with alpelisib as a reference compound. Hit 2 reduced cell viability in both cell lines, but its effect was particularly pronounced in MDA-MB-231 cells, a model of triple-negative breast cancer (TNBC). These results suggest that Hit 2 represents a promising natural scaffold for further design and development in breast cancer therapy, with particular relevance for aggressive TNBC.