Adora1, also known as Adenosine A1 Receptor, is a crucial receptor that binds to adenosine. It plays significant roles in various biological processes, with its functions involving modulation of neurotransmission, immune regulation, and cell growth-related pathways [1-10]. Adenosine binding to Adora1 can lead to activation of multiple downstream signaling cascades, such as the PI3K/AKT pathway, which is associated with cell proliferation and survival [2,3].

In cancer research, tumor Adora1 deletion in human melanoma cell lines in vitro and in immune-deficient xenografts in vivo suppresses cell growth, but it also upregulates PD-L1 levels, inactivating T cells and compromising anti-tumor immunity [1]. In hepatocellular carcinoma, Adora1 is up-regulated in cancer tissues compared to adjacent normal tissue. Overexpression of Adora1 promotes cell proliferation and invasion via the PI3K/AKT pathway, while its knockdown inhibits cell growth and sensitizes cells to chemotherapy [2]. Similar findings are observed in nasopharyngeal carcinoma, where Adora1 overexpression promotes cell proliferation, invasion, and migration, and its silencing has opposite effects [3]. In papillary thyroid carcinoma, Adora1 is overexpressed, correlated with lymph node metastasis and pathological stage, and has diagnostic and prognostic value [4].

In summary, Adora1 is involved in key biological processes, especially in cell growth regulation and immune modulation. Gene-knockout (KO) and conditional-knockout (CKO) mouse models, along with in vitro cell-based functional studies, have been instrumental in revealing its role in cancer progression and immune evasion, highlighting its potential as a therapeutic target in cancer treatment. In addition, studies on Adora1 in other diseases like sepsis-associated acute kidney injury, Parkinson's disease, and Alzheimer's disease further demonstrate its broad-ranging importance in various pathological conditions [5-10].