Ramachandran Ramya, Cannon Marisa, Peshin Supriya, Kundranda Madappa, Scott Aaron J
Department of Internal Medicine, University of Arizona, Tucson, AZ 85724, USA.
College of Medicine, University of Arizona, Tucson, AZ 85724, USA.
Curr Oncol. 2025 Jun 25;32(7):370. doi: 10.3390/curroncol32070370.
Colorectal cancer (CRC) is the third most common malignancy worldwide and the second leading cause of cancer-related mortality in the United States. The incidence of early-onset colorectal cancer (EOCRC) has been increasing over the past several decades. While the etiologies for this rising incidence remain unclear, genetic factors likely play an important role. DNA polymerase epsilon (POLE) mutations occur at a higher rate than average-onset colorectal cancer (AOCRC). DNA polymerase epsilon (Pol ε) is a high-fidelity, processive polymerase that is a promising target for immune checkpoint inhibitors due to its association with various human malignancies, including colorectal cancer. EOCRC remains a major area of focus, and POLE mutations leading to the high-TMB subtype constitute a potential therapeutic target.
结直肠癌（CRC）是全球第三大常见恶性肿瘤，在美国是癌症相关死亡的第二大主要原因。在过去几十年中，早发性结直肠癌（EOCRC）的发病率一直在上升。虽然这种发病率上升的病因尚不清楚，但遗传因素可能起着重要作用。DNA聚合酶ε（POLE）突变的发生率高于平均发病年龄的结直肠癌（AOCRC）。DNA聚合酶ε（Pol ε）是一种高保真、持续合成的聚合酶，由于其与包括结直肠癌在内的各种人类恶性肿瘤有关，是免疫检查点抑制剂的一个有前景的靶点。EOCRC仍然是一个主要的关注领域，导致高肿瘤突变负荷（TMB）亚型的POLE突变构成了一个潜在的治疗靶点。
