Cbx3, also known as HP1γ, is a heterochromatin-associated protein that plays significant roles in multiple biological processes. It is involved in epigenetic regulation, such as histone modifications, and interacts with various key pathways including PI3K/AKT, Ras/KRAS, Wnt/β -catenin, MAPK, Notch, and p53, influencing cell proliferation, apoptosis, and therapy resistance [3].

In glioblastoma, lactate-induced histone lactylation is regulated by Cbx3, leading to immunosuppressive transcriptional programs and immune evasion. Targeting Cbx3 inhibits tumor growth [1]. In prostate cancer, Cbx3 is upregulated in CDK4/6 inhibitor-resistant cells, and a dual BET/PLK1 inhibitor can increase the sensitivity of CRPC cells to CDK4/6 inhibitors partially through Cbx3 [2]. In clear cell renal carcinoma, Cbx3 promotes tumor advancement via PI3K/AKT activation and immunological dysregulation [4]. In colorectal carcinoma, Cbx3 promotes multidrug resistance by suppressing ferroptosis via the CUL3/NRF2/GPX2 axis [5]. In hepatocellular carcinoma, Cbx3 promotes development by regulating cell cycle progression and is regulated by miR-139 [6]. In glioblastoma multiforme, Cbx3 accelerates malignant progression by stabilizing EGFR expression [7].

In conclusion, Cbx3 is a crucial epigenetic regulator involved in multiple biological processes and diseases. Studies using various models, including in vitro and in vivo, have revealed its diverse roles in promoting tumor growth, modulating immune responses, and affecting drug resistance in different cancer types, highlighting its potential as a therapeutic target.