Genetic Alterations of NF-κB and Its Regulators: A Rich Platform to Advance Colorectal Cancer Diagnosis and Treatment.
Genetic Alterations of NF-κB and Its Regulators: A Rich Platform to Advance Colorectal Cancer Diagnosis and Treatment.
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DOI：
10.3390/ijms25010154
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发表时间：
2023-12-21
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
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结直肠癌（CRC）是美国癌症死亡的第三大原因，2023年估计有52，000人死亡。尽管近年来在大肠癌的诊断和治疗方面取得了显著进展，但大肠癌的遗传异质性是大肠癌复发和耐药的罪魁祸首，仍然是一个难以克服的挑战。因此，在新的CRC治疗策略中开发更有效的治疗方法来克服这一挑战势在必行。遗传和表观遗传变化被公认为是CRC恶性肿瘤逐步发展的原因。本文综述了核因子（NF）-κB信号通路的遗传变异信息，包括NF-κB家族成员及其调控因子，如蛋白质精氨酸甲基转移酶5（PRMT 5）、外动力蛋白臂对接复合物亚基2（OPAD 2，也称armadillo repeat-containing 4，ARMC 4）等，在CRC患者中。此外，我们对不同的CRC研究模型提供了深入的见解，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。据估计，NF-κB信号传导组分的遗传改变占cBioportal for Cancer Genomics收集的CRC患者中确定的总体遗传改变的50%以上;因此，强调了其在CRC进展中的至关重要性。因此，NF-κB信号的各种遗传改变可能为CRC的新治疗开发带来巨大希望。未来的努力可以集中于利用CRC模型（例如，PDX或类器官，或等基因人胚胎干细胞（hESC）衍生的结肠细胞，或人多能干细胞（hPSC）衍生的结肠类器官等）进一步揭示结直肠癌进展中NF-κB信号传导中这些遗传改变的基础机制。此外，建立药物发现平台，开发生物银行等，可能会进一步为未来治疗CRC的创新个性化药物的开发铺平道路。
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.
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DOI：
10.1038/s41578-021-00279-y
发表时间：
2021
期刊：
Nature reviews. Materials
影响因子：
--
作者：
Hofer M;Lutolf MP
通讯作者：
Lutolf MP
影响因子：
3.9
作者：
Georges, Laurent M. C.;De Wever, Olivier;Zlobec, Inti
通讯作者：
Zlobec, Inti
影响因子：
29.4
作者：
Boland CR;Goel A
通讯作者：
Goel A
影响因子：
82.9
作者：
Gao, Hui;Korn, Joshua M.;Sellers, William R.
通讯作者：
Sellers, William R.
影响因子：
8
作者：
Chu, Po-Chen;Lin, Peng-Chan;Chen, Ching-Shih
通讯作者：
Chen, Ching-Shih