IGF-II Producing Hepatocellular Carcinoma Treated with Sorafenib: Metabolic Complications and a Foresight to Molecular Targeting Therapy to the IGF Signal.
IGF-II Producing Hepatocellular Carcinoma Treated with Sorafenib: Metabolic Complications and a Foresight to Molecular Targeting Therapy to the IGF Signal.
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DOI：
10.1159/000346462
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发表时间：
2012-09
影响因子：
0.6
通讯作者：
Koike K
中科院分区：
文献类型：
--
作者：
Okushin K;Asaoka Y;Fukuda I;Fujiwara N;Minami T;Sato M;Mikami S;Uchino K;Enooku K;Kondo Y;Tateishi R;Goto T;Shiina S;Yoshida H;Koike K
低血糖是一种罕见的肿瘤患者的副肿瘤表现。低血糖可由多种原因引起，包括降血糖药物的异常增加和肾上腺功能不全。索拉非尼是第一个在治疗晚期肝细胞癌(HCC)中显示出生存益处的药物。这种小分子抑制肿瘤细胞中的丝氨酸/苏氨酸激酶RAF和肿瘤血管中的酪氨酸激酶VEGFR/PDGFR，从而减少肿瘤的生长和血管生成。本文报告一例经索拉非尼治疗后出现严重低血糖的肝细胞癌病例。这种低血糖可能是由两种原因引起的，一种是索拉非尼副作用所致的肾上腺功能不全，另一种是胰岛素样生长因子(IGF)信号的激活，这是由于IGF-II前体未完全加工的过度分泌所致。虽然在某些情况下IGF信号被认为与肝癌的异常生长有关，但还没有其他报道显示索拉非尼对IGF信号活跃的肝癌的影响。不幸的是，索拉非尼在本案中的作用有限。然而，直接抑制IGF信号的新兴药物有望在治疗伴有低血糖的肝细胞癌方面非常有效。
Hypoglycemia is a rare paraneoplastic manifestation of patients with neoplasms. Hypoglycemia can be induced by several causes, including an aberrant increase of hypoglycemic agents and adrenal insufficiency. Sorafenib is the first agent to demonstrate a survival benefit in the treatment of advanced hepatocellular carcinoma (HCC). This small molecule inhibits serine/threonine kinase RAF in tumor cells and tyrosine kinases VEGFR/PDGFR in tumor vasculature and decreases tumor growth and angiogenesis. In this paper, we report a case of HCC who was treated with sorafenib and showed severe hypoglycemia. This hypoglycemia might be induced by two causes, both adrenal insufficiency as an adverse effect of sorafenib and activation of the insulin-like growth factor (IGF) signal by excessive secretion of incompletely processed precursors of IGF-II. Although the IGF signal is suggested to be involved in aberrant growth of HCC in some cases, there is no other report showing the influence of sorafenib on HCC with active IGF signal. Unfortunately, the effect of sorafenib was limited in the present case. However, emerging drugs that directly inhibit the IGF signal can be expected to be highly effective in the treatment of HCC with hypoglycemia.