New Therapeutic Targets Laboratory (TargetsLab) Oncology Unit, Department of Medical Sciences, University of Girona, Girona Institute for Biomedical Research, Emili Grahit 77, Girona 17003, Spain.
Molecules. 2018 Aug 30;23(9):2193. doi: 10.3390/molecules23092193.
Despite advances in breast cancer diagnosis and treatment, many patients still fail therapy, resulting in disease progression, recurrence, and reduced overall survival. Historically, much focus has been put on the intrinsic subtyping based in the presence (or absence) of classical immunohistochemistry (IHC) markers such as estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-related protein (HER2). However, it is widely understood that tumors are composed of heterogeneous populations of cells with a hierarchical organization driven by cancer stem cells (CSCs). In breast tumors, this small population of cells displaying stem cell properties is known as breast CSCs (BCSCs). This rare population exhibit a CD44⁺/CD24 phenotype with high ALDH activity (ALDH⁺), and possesses higher tolerability to chemotherapy, hormone therapy, and radiotherapy and is able to reproduce the bulk of the tumor after reduction of cell populations sensitive to first-line therapy leading to disease relapse. In this review, we present special attention to BCSCs with future directions in the establishment of a therapy targeting this population. Drugs targeting the main BCSCs signaling pathways undergoing clinical trials are also summarized.
尽管乳腺癌的诊断和治疗取得了进展，但许多患者仍未能接受治疗，导致疾病进展、复发和总体生存率降低。从历史上看，人们非常关注基于经典免疫组织化学 (IHC) 标志物（如雌激素受体 (ER)、孕激素受体 (PR) 和人表皮生长因子受体相关蛋白 (HER2)）的内在分型。然而，人们普遍认为肿瘤是由具有分层组织的异质细胞群体组成，这些细胞群体由癌症干细胞 (CSC) 驱动。在乳腺肿瘤中，这种具有干细胞特性的少量细胞被称为乳腺 CSC (BCSC)。这个稀有群体表现出 CD44+/CD24 表型，具有高 ALDH 活性（ALDH+），并且对化疗、激素治疗和放疗具有更高的耐受性，并且能够在减少对一线治疗敏感的细胞群体后复制大部分肿瘤，从而导致疾病复发。在这篇综述中，我们特别关注 BCSC，并提出了针对该群体的治疗方法的未来方向。正在进行临床试验的针对主要 BCSC 信号通路的药物也进行了总结。
