Robert Marie, Frenel Jean-Sébastien, Bourbouloux Emmanuelle, Berton Rigaud Dominique, Patsouris Anne, Augereau Paule, Gourmelon Carole, Campone Mario
a Department of Medical Oncology , Institut de Cancérologie de l'Ouest, René Gauducheau , St. Herblain , France.
b Department of Medical Oncology , Institut de Cancérologie de l'Ouest, Paul Papin , Angers , France.
Expert Opin Pharmacother. 2017 Dec;18(18):2007-2016. doi: 10.1080/14656566.2017.1410139. Epub 2017 Dec 1.
Breast cancer is the most frequent cancer in women. Despite a decline in breast cancer mortality, prognosis of advanced breast cancer remains poor. In a desperate need to improve breast cancer outcomes, newer agents that target molecular pathways are being tested. Deregulation of the phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) is frequently found in breast cancer. This can lead to resistance of endocrine therapy and anti-HER2 therapies. Targeting this pathway may restore sensitivity to these compounds. Buparlisib (BKM-120) is an orally active pan-PI3K inhibitor evaluated in different tumor types. Areas covered: Buparlisib is one of the most investigated PI3K inhibitors. Preclinical and clinical studies of buparlisib in breast cancer are analyzed and discussed. This article reviews the status of buparlisib, completed and ongoing trials, and its safety. Expert opinion: PI3K inhibitors show promising results in breast cancer. However, we raise a number of issues including the identification of biomarkers to predict treatment response and strategies to counteract resistance. Moreover, its toxicity profile could limit its extensive use.
乳腺癌是女性中最常见的癌症。尽管乳腺癌死亡率有所下降，但晚期乳腺癌的预后仍然很差。在迫切需要改善乳腺癌治疗结果的情况下，正在测试针对分子途径的新型药物。磷酸肌醇3-激酶（PI3K）/AKT/哺乳动物雷帕霉素靶蛋白（mTOR）的失调在乳腺癌中经常被发现。这可能导致内分泌治疗和抗HER2治疗的耐药性。靶向该途径可能恢复对这些化合物的敏感性。布帕利昔（BKM-120）是一种口服活性泛PI3K抑制剂，已在不同肿瘤类型中进行评估。涵盖领域：布帕利昔是研究最多的PI3K抑制剂之一。分析和讨论了布帕利昔在乳腺癌中的临床前和临床研究。本文综述了布帕利昔的现状、已完成和正在进行的试验及其安全性。专家意见：PI3K抑制剂在乳腺癌中显示出有前景的结果。然而，我们提出了一些问题，包括预测治疗反应的生物标志物的鉴定以及对抗耐药性的策略。此外，其毒性特征可能会限制其广泛应用。
