PI3Krelated

PI3Krelated refers to topics connected to the phosphoinositide 3-kinase (PI3K) family, a group of lipid kinases that regulate signaling pathways controlling growth, metabolism, survival, and movement in cells. PI3Ks are divided into three main classes (I, II, III), with Class I comprising catalytic subunits such as p110α (PIK3CA), p110β (PIK3CB), p110δ (PIK3CD), and p110γ (PIK3CG). These catalytic units associate with regulatory subunits (for example, p85 family proteins) to form active holoenzymes. Class II and III PI3Ks have distinct subunit compositions and roles, including membrane trafficking and autophagy regulation.

In canonical signaling, PI3K phosphorylates phosphatidylinositol-4,5-bisphosphate (PIP2) to generate phosphatidylinositol-3,4,5-trisphosphate (PIP3), which recruits PH-domain–containing proteins such as AKT and PDK1 to the plasma membrane. This leads to activation of the AKT/mTOR pathway and other downstream effectors, ultimately influencing cell growth, metabolism, survival, and differentiation. PI3K signaling is activated by growth factors, insulin, and immune signals, and is tightly regulated by phosphatases such as PTEN.

Clinical relevance is broad. PI3K pathway mutations and amplifications are common in cancer, with PIK3CA alterations being particularly frequent. Inhibitors targeting specific PI3K isoforms are used in oncology (for example, alpelisib as a PI3Kα inhibitor; idelalisib for PI3Kδ; duvelisib for PI3Kδ/γ) and in some immune-mediated diseases. Somatic PI3K alterations also underlie overgrowth and vascular malformation syndromes (collectively referred to as PI3K-related disorders). Ongoing research explores resistance mechanisms and combination strategies to improve efficacy and safety.