Martí R M, Sorolla A, Yeramian A
Servicio de Dermatología, Hospital Universitari Arnau de Vilanova, Universitat de Lleida, IRBLLEIDA, Lleida, Spain.
Actas Dermosifiliogr. 2012 Sep;103(7):579-90. doi: 10.1016/j.ad.2011.08.009. Epub 2012 Jan 20.
Research into molecular targets for drug development in melanoma is starting to bear fruit. Of the drugs tested to date in patients with metastatic melanoma, those that have yielded the best results are V600E BRAF inhibitors in melanomas carrying the V600E mutation; c-kit tyrosine kinase activity inhibitors in melanomas carrying c-kit mutations; and anti-cytotoxic T lymphocyte antigen 4 (CTLA-4) antibodies, which block the mechanisms involved in immune tolerance. Many problems have yet to be resolved in these areas, however, such as the rapid development of resistance to BRAF and c-kit inhibitors and the lack of biomarkers to predict treatment response in the case of CTLA-4 blockers. We review the results of targeted therapy with these and other drugs in metastatic melanoma and discuss what the future holds for this field.
黑色素瘤药物开发分子靶点的研究开始取得成果。在转移性黑色素瘤患者中迄今为止所测试的药物中,产生最佳效果的药物是:携带V600E突变的黑色素瘤中的V600E BRAF抑制剂;携带c-kit突变的黑色素瘤中的c-kit酪氨酸激酶活性抑制剂;以及抗细胞毒性T淋巴细胞抗原4(CTLA-4)抗体,其阻断免疫耐受所涉及的机制。然而,这些领域仍有许多问题有待解决,比如对BRAF和c-kit抑制剂耐药性的快速出现,以及在CTLA-4阻断剂治疗情况下缺乏预测治疗反应的生物标志物。我们回顾了这些及其他药物在转移性黑色素瘤中进行靶向治疗的结果,并讨论了该领域的未来发展。