PI3K is a signaling pathway component, also known as phosphoinositide 3-kinase, that functions in the b7 h3-activated and lrg1-driven pi3k/AKT signaling axis and is inhibited by ponatinib. Its primary mechanism here is as a kinase pathway node whose sustained inhibition can reshape immune cell fate, with stable and sustained suppression being essential for CD8+ T stem cell memory cell (TSCM) induction. In cancer biology, PI3K signaling is implicated in tumor progression and the tumor microenvironment, while in metastasis it mediates LRG1-induced neutrophil extracellular trap formation through the TGFBR/PI3K/AKT axis. Recent studies also highlight PI3K as a therapeutic target of off-target ponatinib activity, linking kinase inhibition to enhanced TSCM development. Overall, the literature positions PI3K as a central signaling hub in immunology, metastasis, and oncogenic signaling, with pathway inhibition emerging as a mechanistically important intervention.
Immunology and T cell memory
- Ponatinib was shown to inhibit pi3k signaling, and sustained inhibition was required for CD8+ TSCM induction. (PMID:41946709)
- A 2026 Nature Communications study reported that ponatinib inhibits LCK and PI3K signaling to promote CD8+ T stem cell memory cell development. (PMID:41946709)
Metastasis and neutrophil extracellular traps
- lrg1 promotes liver metastasis through a TGFBR/PI3K/AKT axis that drives neutrophil extracellular trap formation. (PMID:41963620)
- PI3K is a signaling kinase pathway component in the LRG1-associated axis mediating neutrophil extracellular trap formation. (PMID:41963620)
- A 2026 Cellular & Molecular Immunology paper linked hepatocyte-derived LRG1 to liver premetastatic niche formation and impaired immunotherapy via this pathway. (PMID:41963620)
Cancer and tumor progression
- b7 h3 activates PI3K pathways in the context of tumor progression. (PMID:41964005)
- A 2026 Cell Communication and Signaling review described B7-H3 (CD276) as part of exosome biogenesis and the tumor microenvironment, highlighting PI3K-linked signaling as a therapeutic nexus. (PMID:41964005)
- PI3K signaling was specifically noted as a pathway component activated by B7-H3 during tumor progression. (PMID:41964005)