Saba Raya, Alsayed Alhareth, Zacny James P, Dudek Arkadiusz Z
Presence Saint Joseph Hospital, 2900 North Lakeshore Drive, Chicago, IL 60657, USA.
University of Illinois Hospital and Health Sciences System, UI Cancer Center, Medical Center Administration Building (M/C 700), 914 South Wood Street, Chicago, IL 60612, USA.
Int J Breast Cancer. 2016;2016:9768183. doi: 10.1155/2016/9768183. Epub 2016 Jan 31.
The Forkhead box M1 (FOXM1) is a transcription factor that has been implicated in normal cell growth and proliferation through control of cell cycle transition and mitotic spindle. It is implicated in carcinogenesis of various malignancies where it is activated by either amplification, increased stability, enhanced transcription, dysfunction of regulatory pathways, or activation of PI3K/AKT, epidermal growth factor receptor, Raf/MEK/MAPK, and Hedgehog pathways. This review describes the role of FOXM1 in breast cancer. This includes how FOXM1 impacts on different subtypes of breast cancer, that is, luminal/estrogen receptor positive (ER+), expressing human epidermal growth factor receptor 2 (HER2), basal-like breast cancer (BBC), and triple negative breast cancer (TNBC). The review also describes different tested preclinical therapeutic strategies targeting FOXM1. Developing clinically applicable therapies that specifically inhibit FOXM1 activity is a logical next step in biomarker-driven approaches against breast cancer but will not be without its challenges due to the unique properties of this transcription factor.
叉头框M1(FOXM1)是一种转录因子,通过控制细胞周期转换和有丝分裂纺锤体参与正常细胞生长和增殖。它与多种恶性肿瘤的致癌作用有关,在这些肿瘤中,它通过扩增、稳定性增加、转录增强、调节途径功能障碍或PI3K/AKT、表皮生长因子受体、Raf/MEK/MAPK和Hedgehog途径的激活而被激活。本综述描述了FOXM1在乳腺癌中的作用。这包括FOXM1如何影响乳腺癌的不同亚型,即管腔型/雌激素受体阳性(ER+)、表达人表皮生长因子受体2(HER2)、基底样乳腺癌(BBC)和三阴性乳腺癌(TNBC)。该综述还描述了针对FOXM1的不同经测试的临床前治疗策略。开发特异性抑制FOXM1活性的临床适用疗法是生物标志物驱动的乳腺癌治疗方法的合理下一步,但由于这种转录因子的独特性质,这并非没有挑战。