PIK3CG (Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Gamma)

These results indicate that PI3Kγ contributes to cSCC development not by directly driving tumour cell proliferation but by shaping an immunosuppressive tumour microenvironment. Targeting PI3Kγ may therefore represent a promising immunotherapeutic strategy to enhance cytotoxic T-cell-mediated antitumour immunity in cSCC.

Together, these structure-informed alleles show that discrete PI3K structural perturbations can differentially uncouple lifespan, growth, and developmental outcomes in vivo . By combining structural modeling with genome editing in a tractable aging model, this work establishes a framework for dissecting conserved signaling enzymes at single-residue resolution and uncovers unexpected organismal roles for PI3K structure in coordinating growth and longevity.

This review summarizes the mechanisms by which TAMs and CAFs contribute to resistance to ICIs and TKIs and discusses therapeutic strategies under active investigation targeting these stromal components-including inhibition of TGF-β, IL-6, and HGF/MET pathways, TAM reprogramming via PI3Kγ or CD47 blockade, and CAF depletion using FAP-targeted approaches. Targeting the TME holds promise for overcoming therapeutic resistance and improving clinical outcomes in advanced HCC, warranting further evaluation in well-designed clinical trials.

GBM comprise three functional TIME subtypes with divergent vascular-immune landscapes that require subtype-specific therapeutic strategies. TIME-med tumors are most amenable to immunotherapies. TIME-low tumors derive transient effects with anti-angiogenic immunomodulating therapies, and TIME-high are resistant or even experience worse outcome without targeted reversal of myeloid immunosuppression.

Our findings highlight the critical role of PI3K-γ signaling in postoperative sx-MDSC-mediated immune suppression. Targeting this pathway with PI3K-γ inhibitors represents a promising therapeutic strategy to prevent NK cell suppression and reduce postoperative metastases.

We outline current and emerging myeloid-reprogramming strategies-including PI3Kγ and CSF1-CSF1R targeting, TREM2 antagonism, COX-2-PGE2 blockade, and adenosine-axis inhibition-and their integration with PD-(L)1 therapy, alongside single-cell/spatial endpoints to quantify on-treatment remodeling. The purpose of this mini-review is to provide a mechanistic and technology-informed framework to reference rational trial design and clinical translation for overcoming checkpoint resistance in CRC.

Our study reveals a novel mechanism by which PIK3CG-KD regulates Gln metabolism and mitochondrial function via the S6K2/P53/GLS2 axis, providing a rationale for metabolic intervention and precision therapy in PIK3CG-deficient PDAC.

The DUV-NCs were found to be safe in toxicity studies with no major alterations in biomarkers compared to the control. In conclusion, DUV-NCs is a promising strategy to deliver DUV in hematological malignancies with improved efficacy and safety.

Molecular docking further indicated that isoledene and β-himachalene exhibit the highest predicted affinity for PI3Kγ, suggesting a potential involvement of PI3K-related signaling in the pro-apoptotic activity of CAEO. Together, these results suggest that CAEO induces apoptosis through a mitochondria-mediated mechanism.

Our synthesis provides an appraisal of the evolving landscape of myeloid-informed precision immuno-oncology in HNSCC and outlines pragmatic standards and avenues for clinical translation. We hope these insights will assist researchers and clinicians as they endeavor to implement more effective, individualized regimens.

It was more potent than 5-fluorouracil in SW620 cells (IC50 = 21.7 μM)...Overall, compound 14 significantly outperformed the original hit (STL427944), achieving FOXM1 inhibition at <12.5 μM (vs. 25-50 μM for STL). This marks it as a next-generation FOXM1-targeting lead, combining potent and selective anticancer activity with sustainable synthesis, and positioning it as a strong candidate for further preclinical development.

Additionally, we employed pexidartinib and tenalisib to evaluate TAMs reversal in the iTC-OS-on-a-chip model by selectively inhibiting CSF1R and PI3Kγ, respectively. TAMs reprogramming from tumor promoting M2 to tumor suppressing M1 phenotype is confirmed through gene expression analysis of M1 (CCR7, IL-1β, IL-6) and M2 (CD206, CD163, IL-10) macrophage markers, alongside quantification of secreted cytokines via ELISA assay. This advanced iTC-OS-on-a-chip model offers a robust platform for investigating OS-immune cell interactions, enabling pre-clinical evaluation of chemo/immunotherapeutics and improving the translational relevance in OS research.