Targeted therapies for hepatocellular carcinoma.
Targeted therapies for hepatocellular carcinoma.
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DOI：
10.1053/j.gastro.2011.03.006
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发表时间：
2011-05
期刊：
影响因子：
29.4
通讯作者：
Llovet JM
中科院分区：
文献类型：
--
作者：
Villanueva A;Llovet JM
与大多数实体瘤不同，过去十年，美国和欧洲的肝细胞癌 (HCC) 发病率和死亡率有所增加。大多数患者在诊断时已处于晚期，因此迫切需要新的全身疗法。索拉非尼是一种酪氨酸激酶抑制剂 (TKI)，已证明对 HCC 患者具有临床疗效。对肺癌、乳腺癌或结直肠癌患者的研究表明，肿瘤内癌细胞的遗传异质性影响其对针对特定分子的治疗的反应。当肿瘤进展需要改变特定癌基因（癌基因成瘾）时，选择性阻断其产物的药物可能会减缓肿瘤生长。然而，目前尚无特定的癌基因改变与 HCC 进展有关，因此提高我们对其分子发病机制的理解非常重要。目前有许多评估 TKI 治疗 HCC 的临床试验，包括与索拉非尼（例如厄洛替尼）联合使用或与索拉非尼（例如利尼凡尼）作为一线疗法进行比较的试验。对于对索拉非尼没有反应或不耐受的患者，正在测试布立尼布、依维莫司和单克隆抗体（例如雷莫芦单抗）等 TKI 作为二线疗法。目前正在进行早期试验，调查多达 60 种试剂对 HCC 的疗效。总之，这些研究可能会改变 HCC 的治疗策略，并且可能会为晚期 HCC 患者开发联合疗法。介导 HCC 进展的癌基因的鉴定，以及将其产品作为生物标志物进行监测的试验，可能会导致个性化治疗；干扰 HCC 进展所需信号通路的试剂可用于治疗选定人群，从而最大限度地提高疗效和成本效益。
Unlike most solid tumors, incidence and mortality of hepatocellular carcinoma (HCC) have increased in the US and Europe in the last decade. Most patients are diagnosed at advanced stages, so there is an urgent need for new systemic therapies. Sorafenib, a tyrosine kinase inhibitor (TKI), has demonstrated clinical efficacy in patients with HCC. Studies in patients with lung, breast, or colorectal cancers indicated that the genetic heterogeneity of cancer cells within a tumor affect its response to therapeutics designed to target specific molecules. When tumor progression requires alterations in specific oncogenes (oncogene addiction), drugs that selectively block their products might slow tumor growth. However, no specific oncogene alterations are yet known to be implicated in HCC progression, so it is important to improve our understanding of its molecular pathogenesis. There are currently many clinical trials evaluating TKIs for HCC, including those tested in combination with (e.g., erlotinib) or compared to (e.g., linifanib) sorafenib as a first-line therapy. For patients that do not respond or are intolerant to sorafenib, TKIs such as brivanib, everolimus, and monoclonal antibodies (e.g. ramucirumab) are being tested as second-line therapies. There are early-stage trials investigating the efficacy for up to 60 reagents for HCC. Together, these studies might change the management strategy for HCC, and combination therapies might be developed for patients with advanced HCC. Identification of oncogenes that mediate progression of HCC, and trials that monitor their products as biomarkers, might lead to personalized therapy; reagents that interfere with signaling pathways required for HCC progression might be used to treat selected populations, and thereby maximize the efficacy and cost-benefit.
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影响因子：
11.2
作者：
Hoshida Y;Nijman SM;Kobayashi M;Chan JA;Brunet JP;Chiang DY;Villanueva A;Newell P;Ikeda K;Hashimoto M;Watanabe G;Gabriel S;Friedman SL;Kumada H;Llovet JM;Golub TR
通讯作者：
Golub TR
影响因子：
51.1
作者：
Faivre, Sandrine;Raymond, Eric;Cheng, Ann Lii
通讯作者：
Cheng, Ann Lii
索拉非尼对亚太地区晚期肝细胞癌患者的疗效和安全性：一项 III 期随机、双盲、安慰剂对照试验
影响因子：
51.1
作者：
Cheng, Ann-Lii;Kang, Yoon-Koo;Guan, Zhongzhen
通讯作者：
Guan, Zhongzhen
影响因子：
45.3
作者：
Abou-Alfa, Ghassan K.;Schwartz, Lawrence;Saltz, Leonard B.
通讯作者：
Saltz, Leonard B.
影响因子：
25.7
作者：
Croswell, Jennifer M.;Kramer, Barnett S.
通讯作者：
Kramer, Barnett S.