Department of Pharmacology & Toxicology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indianapolis, IN 46202, USA.
Int J Mol Sci. 2023 Dec 21;25(1):154. doi: 10.3390/ijms25010154.
Colorectal cancer (CRC) is the third leading cause of cancer mortality in the United States, with an estimated 52,000 deaths in 2023. Though significant progress has been made in both diagnosis and treatment of CRC in recent years, genetic heterogeneity of CRC-the culprit for possible CRC relapse and drug resistance, is still an insurmountable challenge. Thus, developing more effective therapeutics to overcome this challenge in new CRC treatment strategies is imperative. Genetic and epigenetic changes are well recognized to be responsible for the stepwise development of CRC malignancy. In this review, we focus on detailed genetic alteration information about the nuclear factor (NF)-κB signaling, including both NF-κB family members, and their regulators, such as protein arginine methyltransferase 5 (PRMT5), and outer dynein arm docking complex subunit 2 (ODAD2, also named armadillo repeat-containing 4, ARMC4), etc., in CRC patients. Moreover, we provide deep insight into different CRC research models, with a particular focus on patient-derived xenografts (PDX) and organoid models, and their potential applications in CRC research. Genetic alterations on NF-κB signaling components are estimated to be more than 50% of the overall genetic changes identified in CRC patients collected by cBioportal for Cancer Genomics; thus, emphasizing its paramount importance in CRC progression. Consequently, various genetic alterations on NF-κB signaling may hold great promise for novel therapeutic development in CRC. Future endeavors may focus on utilizing CRC models (e.g., PDX or organoids, or isogenic human embryonic stem cell (hESC)-derived colonic cells, or human pluripotent stem cells (hPSC)-derived colonic organoids, etc.) to further uncover the underpinning mechanism of these genetic alterations in NF-κB signaling in CRC progression. Moreover, establishing platforms for drug discovery in dishes, and developing Biobanks, etc., may further pave the way for the development of innovative personalized medicine to treat CRC in the future.
结直肠癌（CRC）是美国癌症死亡的第三大主要原因，预计 2023 年将有 52000 人死亡。尽管近年来在 CRC 的诊断和治疗方面取得了重大进展，但 CRC 的遗传异质性——可能导致 CRC 复发和耐药的罪魁祸首，仍然是一个无法逾越的挑战。因此，开发更有效的治疗方法来克服新 CRC 治疗策略中的这一挑战至关重要。遗传和表观遗传变化被认为是 CRC 恶性肿瘤逐步发展的原因。在这篇综述中，我们重点介绍了核因子（NF）-κB 信号转导的详细遗传改变信息，包括 NF-κB 家族成员及其调节剂，如精氨酸甲基转移酶 5（PRMT5）和外动力蛋白臂对接复合物亚基 2（ODAD2，也称为棘皮动物重复蛋白 4，ARMC4）等，在 CRC 患者中的信息。此外，我们深入了解了不同的 CRC 研究模型，特别关注患者来源的异种移植物（PDX）和类器官模型，以及它们在 CRC 研究中的潜在应用。通过 cBioportal for Cancer Genomics 收集的 CRC 患者的整体遗传变化中，NF-κB 信号转导组件的遗传改变估计超过 50%；因此，强调了其在 CRC 进展中的重要性。因此，NF-κB 信号转导的各种遗传改变可能为 CRC 的新型治疗开发带来巨大希望。未来的研究可能集中在利用 CRC 模型（例如 PDX 或类器官，或同源人类胚胎干细胞（hESC）衍生的结肠细胞，或人类多能干细胞（hPSC）衍生的结肠类器官等），进一步揭示这些遗传改变在 CRC 进展中 NF-κB 信号转导的潜在机制。此外，建立药物发现平台和开发生物库等，可能为未来开发创新的个性化药物治疗 CRC 铺平道路。
Int J Mol Sci. 2021-7-11
Int J Mol Sci. 2020-5-23
Clin Cancer Res. 2017-9-14
Biomed Pharmacother. 2018-3
Int J Mol Sci. 2025-7-3
Cell Death Discov. 2025-1-28
Eur J Med Res. 2024-12-19
Int J Mol Sci. 2024-11-24
Oncol Lett. 2023-6-15
Int J Mol Sci. 2023-3-23
Genes Dis. 2022-4-13
CA Cancer J Clin. 2023-1
Animal Model Exp Med. 2023-2
World J Gastroenterol. 2022-9-7
Zotero 插件
