Pik3cg, encoding phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit γ (Pi3kγ), is a key component in the phosphoinositide-3-kinase (PI3K) signaling pathway. This pathway is involved in various cellular functions such as cell growth, survival, and metabolism [3,4,5,6,7]. Genetic models, like KO or CKO mouse models, are valuable for studying Pik3cg's function in different biological contexts.

In septic myocardial injury, Pik3cg activates NLRP3 inflammasomes, promoting pyroptosis. Inhibition of Pik3cg by siRNA or the inhibitor AS-604850 reversed the pyroptosis-related changes induced by cecal ligation and puncture in mice [1]. In acute leukemia, a high-risk subset shows a selective dependency on the PI3Kγ complex involving Pik3cg. The selective PI3Kγ inhibitor eganelisib, alone or combined with cytarabine, is effective in treating leukemia [2]. In metastatic prostate cancer, Pik3cg is highly expressed, and its pharmacologic inhibition blocks tumor cell growth, reverses epithelial-mesenchymal transition, and reduces metastasis [3]. In claudin-low breast cancer, targeting Pik3cg enhances the growth-inhibitory and apoptosis-promoting effects of paclitaxel [4]. In acute myeloid leukemia, suppression of the PIK3CG-PIK3R5 axis inhibits Akt signaling and compromises cell fitness, and a PROTAC molecule that degrades Pik3cg potently suppresses AML progression [5]. In multiple myeloma, inhibition of Pik3cg suppresses cell growth via the c-Myc pathway and enhances sensitivity to chemotherapy [6].

In conclusion, Pik3cg plays crucial roles in multiple disease conditions including septic myocardial injury, leukemia, prostate cancer, breast cancer, and multiple myeloma. The use of KO/CKO mouse models and other loss-of-function experiments has significantly contributed to revealing Pik3cg's functions in these diseases, suggesting it as a potential therapeutic target in these areas.