Progress of poly (ADP-ribose) polymerase inhibitors in treatment of colorectal cancer
宋明瀚 1邵丽娟 2陈斯泽 3杨璐
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作者信息
1. 广东药科大学附属第一医院肿瘤免疫科,广州 510080
2. 广东省普通高校肿瘤免疫治疗重点实验室,广州 510080
3. 广东省食管癌精准治疗工程技术研究中心,广州 510080
折叠
摘要
结直肠癌恶性程度高,尽管在化疗基础上采用靶向药物治疗提高了疗效,晚期结直肠癌患者预后仍较差。聚二磷酸腺苷核糖聚合酶(PARP)抑制剂作为第一个协同致死机制类靶向药物,在同源重组缺陷的卵巢癌、乳腺癌中应用广泛,取得较好的临床效果。近些年来,随着二代测序技术的进步和精准靶向治疗日渐成熟,越来越多的临床试验开始探索PARP抑制剂在结直肠癌中的应用。文章阐述了PARP抑制剂治疗结直肠癌的相关分子机制及几种联合PARP抑制剂治疗方案在结直肠癌领域的应用,以期为晚期结直肠癌治疗提供新思路。 Colorectal cancer is a highly malignant disease characterized by a poor prognosis. Although the targeted therapy based on chemotherapy improves the efficacy, the prognosis of advanced colorectal cancer patients is poor. Poly (ADP-ribose) polymerase (PARP) inhibitors, which act through a synergistic lethal mechanism, have been widely utilized in treating ovarian and breast cancer cases with homologous recombination deficiency and have demonstrated positive clinical outcomes. Recently, due to advancements in next-generation sequencing technology and the development of precision targeted therapy, an increasing number of clinical trials have started to investigate the potential of PARP inhibitors in colorectal cancer treatment. This review summarized the molecular mechanism of PARP inhibitors in the treatment of colorectal cancer and the application of several combined PARP inhibitors therapy regimens in colorectal cancer, in order to provide new insights for the treatment of colorectal cancer.
Abstract
Colorectal cancer is a highly malignant disease characterized by a poor prognosis. Although the targeted therapy based on chemotherapy improves the efficacy, the prognosis of advanced colorectal cancer patients is poor. Poly (ADP-ribose) polymerase (PARP) inhibitors, which act through a synergistic lethal mechanism, have been widely utilized in treating ovarian and breast cancer cases with homologous recombination deficiency and have demonstrated positive clinical outcomes. Recently, due to advancements in next-generation sequencing technology and the development of precision targeted therapy, an increasing number of clinical trials have started to investigate the potential of PARP inhibitors in colorectal cancer treatment. This review summarized the molecular mechanism of PARP inhibitors in the treatment of colorectal cancer and the application of several combined PARP inhibitors therapy regimens in colorectal cancer, in order to provide new insights for the treatment of colorectal cancer.