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舒尼替尼为黑色素瘤治疗带来新希望

2012-03-12 MedSci MedSci原创

近日,来自国外的研究人员表示,他们发现了一种可以治疗转移性黑色素瘤的新方法,相关的研究成果于近日刊登在了国际癌症杂志Journal of Clinical Cancer Research上。 药物舒尼替尼(sunitinib)已经获得FDA批准用于治疗肾脏癌症和胃肠间质癌症,然而在舒尼替尼二期临床试验中发现,这种药物可以对治疗黑色素瘤有一定帮助,但是只是对于皮肤接受不到太阳光照射的身体部分有一定

近日,来自国外的研究人员表示,他们发现了一种可以治疗转移性黑色素瘤的新方法,相关的研究成果于近日刊登在了国际癌症杂志Journal of Clinical Cancer Research上。

药物舒尼替尼(sunitinib)已经获得FDA批准用于治疗肾脏癌症和胃肠间质癌症,然而在舒尼替尼二期临床试验中发现,这种药物可以对治疗黑色素瘤有一定帮助,但是只是对于皮肤接受不到太阳光照射的身体部分有一定帮助,比如口腔粘膜表面、足底、手掌心等。“黑色素瘤这种皮肤癌症很难治疗,用目前最标准的化学疗法根本无法治疗,毫无效果,”研究者David Minor博士表示。他还表示,他们这项研究揭示了单一介质的化学疗法只能够对于5%-20%的病人产生应答率,但是如果能够产生50%以上的应答率就是一个很大的进步了。

实验中所研究的黑色素瘤疾病都有着这样的一个共性,就是基因KIT的突变,该基因是编码酪氨酸激酶受体的基因,该基因突变之后产生了一种不正常的蛋白质,这种畸形蛋白质可以促使癌细胞的增殖,然而Sunitinib的作用便是阻止这种畸形蛋白来发挥作用,从而抑制癌细胞生长。

研究人员检测了10个IIII期转移性黑色素瘤患者体内Sunitinib所起的作用(KIT基因突变),其中4个人能够完成实验的流程,三个患者可以对药物进行有效反应,另外一个患者疾病的肝转移效应消失了长达15个月,另外两个患者在实验进行到7个月和1个月的时候就放弃了。研究者表示,我们必须提高警惕,尤其是对于试验中的小部分患者,结果令人激动人心,因为患者最终试验的结果比用化学疗法治疗的效果好很多。

研究者表示,黑色素瘤,和很多癌症一样,在不同人群中是不一样的,而且突变的基因也是不同的,通过识别哪些KIT基因突变的患者,我们可以用 Sunitinib来治疗,但是如果不是KIT基因突变的话,作用效果就不太理想。由于Sunitinib已经进行了大量的实验验证,这种药物的副作用包括疲劳、血细胞数量降低、焦虑等,但是使用此药物后,相信大部分患者都是可以克服的。

研究者下一步是将Sunitinib进行大批量的实验,甚至不光是对4期患者进行实验,也可以用于对早期发现的患者进行试验来验证此药物的疗效。

Sunitinib Therapy for Melanoma Patients with KIT Mutations

David R. Minor1, Mohammed Kashani-Sabet1, Maria Garrido2, Steven J. O'Day3, Omid Hamid3, and Boris C. Bastian2

Purpose: Recent studies have shown activating KIT mutations in melanoma originating from mucosa, acral, or cumulative sun-damaged skin sites. We aimed to assess the predictive role of KIT mutation, amplification, or overexpression for response to treatment with the kinase inhibitor sunitinib. Experimental Design: Tumor tissues from 90 patients with stage III or IV acral, mucosal, or cumulative sun-damaged skin melanoma underwent sequencing of KIT, BRAF, NRAS, and GNAQ genes, FISH analysis for KIT amplification, and immunohistochemistry of KIT protein (CD117). Patients with mutations, amplifications, or overexpression of KIT were treated with sunitinib and responses measured by Response Evaluation Criteria in Solid Tumors (RECIST). Results: Eleven percent of the melanomas tested had mutations in KIT, 23% in BRAF, 14% in NRAS, and none in GNAQ. Of 12 patients treated with sunitinib, 10 were evaluable. Of the 4 evaluable patients with KIT mutations, 1 had a complete remission for 15 months and 2 had partial responses (1- and 7-month duration). In contrast, only 1 of the 6 patients with only KIT amplification or overexpression alone had a partial response. In 1 responder with rectal melanoma who later progressed, the recurring tumor had a previously undetected mutation in NRAS, which was found in addition to the persisting mutation in KIT. Interestingly, among patients with manifest stage IV disease, KIT mutations were associated with a significantly shortened survival time (P < 0.0001). Conclusions: Sunitinib may have activity in patients with melanoma and KIT mutations; more study is needed. KIT mutations may represent an adverse prognostic factor in metastatic melanoma.

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    2012-04-14 sunylz
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    2012-06-07 珙桐
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