Generic chemoprevention of hepatocellular carcinoma.
Generic chemoprevention of hepatocellular carcinoma.
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DOI：
10.1111/nyas.13971
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发表时间：
2019-03
影响因子：
5.2
通讯作者：
Hoshida Y
中科院分区：
文献类型：
--
作者：
Athuluri-Divakar SK;Hoshida Y
由病毒或代谢病因引起的慢性纤维化肝病是发展为肝细胞癌（HCC）的高风险状况。即使在早期HCC肿瘤的治愈性治疗后，致癌微环境仍然存在于残留的患病肝脏中，并支持原发性HCC肿瘤的发展（原发性HCC复发）。因此，在不仅有第一原发性肝癌肿瘤风险而且有第二原发性肝癌肿瘤风险的患者中预防肝癌发展在理论上是改善患者预后的最有效策略。然而，迄今为止还没有建立这种疗法。一个主要的挑战是识别临床相关的目标，这可以通过利用化学预防发现的反向工程策略来实现，将来自临床队列的组学信息与癌症发展的完整随访相结合。临床和实验研究已经提出了病因特异性和通用候选HCC化学预防策略，包括他汀类药物、抗糖尿病药物、选择性分子靶向药物以及饮食和营养物质。候选化合物的临床测试可以通过将其与HCC风险生物标志物评估相结合来经济有效地进行，以指定最有可能从治疗中受益的目标患者人群。无毒的仿制药将在各种HCC病因和临床背景中具有广泛的临床适用性，并有望大幅改善HCC仍然令人沮丧的预后。
Chronic fibrotic liver disease caused by viral or metabolic etiologies is a high-risk condition for developing hepatocellular carcinoma (HCC). Even after curative treatment of early-stage HCC tumor, the carcinogenic microenvironment persists in the remnant diseased liver and supports development of de novo HCC tumors (de novo HCC recurrence). Therefore, prevention of HCC development in patients at risk of not only first primary but also second primary HCC tumors is theoretically the most impactful strategy to improve patient prognosis. However, no such therapy has been established to date. One major challenge is identification of clinically relevant targets, which can be achieved by utilizing the reverse-engineering strategy of chemoprevention discovery, integrating omics information from clinical cohorts with completed follow-up for cancer development. Clinical and experimental studies have suggested etiology-specific and generic candidate HCC chemoprevention strategies, including statins, antidiabetic drugs, selective molecular targeted agents, and dietary and nutritional substances. Clinical testing of the candidate compounds can be cost-effectively performed by combining it with HCC risk biomarker evaluation to specify the target patient population most likely benefit from the therapy. Non-toxic, generic agents will have broad clinical applicability across the diverse HCC etiologies and clinical contexts, and are expected to substantially improve the still dismal prognosis of HCC.
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影响因子：
11.2
作者：
Cao Z;Fan-Minogue H;Bellovin DI;Yevtodiyenko A;Arzeno J;Yang Q;Gambhir SS;Felsher DW
通讯作者：
Felsher DW
影响因子：
3.8
作者：
Ballestri S;Nascimbeni F;Baldelli E;Marrazzo A;Romagnoli D;Lonardo A
通讯作者：
Lonardo A
影响因子：
13.5
作者：
Aleksandrova, Krasimira;Boeing, Heiner;Noethlings, Ute;Jenab, Mazda;Fedirko, Veronika;Kaaks, Rudolf;Lukanova, Annekatrin;Trichopoulou, Antonia;Trichopoulos, Dimitrios;Boffetta, Paolo;Trepo, Elisabeth;Westhpal, Sabine;Duarte-Salles, Talita;Stepien, Magdalena;Overvad, Kim;Tjonneland, Anne;Halkjaer, Jytte;Boutron-Ruault, Marie-Christine;Dossus, Laure;Racine, Antoine;Lagiou, Pagona;Bamia, Christina;Benetou, Vassiliki;Agnoli, Claudia;Palli, Domenico;Panico, Salvatore;Tumino, Rosario;Vineis, Paolo;Bueno-De-Mesquita, Bas;Peeters, Petra H.;Gram, Inger Torhild;Lund, Eiliv;Weiderpass, Elisabete;Quiros, J. Ramon;Agudo, Antonio;Sanchez, Maria-Jose;Gavrila, Diana;Barricarte, Aurelio;Dorronsoro, Miren;Ohlsson, Bodil;Lindkvist, Bjoern;Johansson, Anders;Sund, Malin;Khaw, Kay-Tee;Wareham, Nicholas;Travis, Ruth C.;Riboli, Elio;Pischon, Tobias
通讯作者：
Pischon, Tobias
影响因子：
24.5
作者：
Chen, Hsiao-Ping;Shieh, Jeng-Jer;Wu, Chun-Ying
通讯作者：
Wu, Chun-Ying
P62/SQSTM1与维生素D受体结合抑制肝星细胞活性，纤维化和肝癌。
影响因子：
50.3
作者：
Duran A;Hernandez ED;Reina-Campos M;Castilla EA;Subramaniam S;Raghunandan S;Roberts LR;Kisseleva T;Karin M;Diaz-Meco MT;Moscat J
通讯作者：
Moscat J