Hon Jane Date C, Singh Baljit, Sahin Aysegul, Du Gang, Wang Jinhua, Wang Vincent Y, Deng Fang-Ming, Zhang David Y, Monaco Marie E, Lee Peng
Department of Pathology, Rutgers Robert Wood Johnson Medical School Piscataway, NJ, USA.
Department of Pathology, New York University School of Medicine New York, NY, USA.
Am J Cancer Res. 2016 Sep 1;6(9):1864-1872. eCollection 2016.
Treatment protocols for breast cancer depend predominantly on receptor status with respect to estrogen (estrogen receptor alpha), progesterone (progesterone receptor) and human epidermal growth factor [human epidermal growth factor receptor 2 (HER2)]. The presence of one or more of these receptors suggests that a treatment targeting these pathways might be effective, while the absence of, or in the case of HER2, lack of overexpression of, all of these receptors, termed triple negative breast cancer (TNBC), indicates a need for the more toxic chemotherapy. In an effort to develop targeted therapies for TNBC, it will be necessary to differentiate among specific TNBC subtypes. The subset of TNBC that expresses androgen receptor (AR) has been determined to express genes consistent with a luminal subtype and therefore may be amenable to therapies targeting either AR, itself, or other pathways typical of a luminal subtype. Recent investigations of the AR signal pathway within breast cancer lead to AR as a significant target for breast cancer therapy with several clinical trials currently in progress. The subclass of TNBC that lacks AR, which we have termed quadruple negative breast cancer (QNBC) currently lacks a defined targetable pathway. Unlike AR-positive TNBC, QNBC predominantly exhibits a basal-like molecular subtype. Several subtypes and related pathway proteins are preferentially expressed in QNBC that may serve as effective targets for treatment, such as ACSL4, SKP2 and EGFR. ACSL4 expression has been demonstrated to be inversely correlated with expression of hormone/growth factor receptors and may thus serve as a biomarker for QNBC as well as a target for therapy. In the following review we summarize some of the current efforts to develop alternatives to chemotherapy for TNBC and QNBC.
乳腺癌的治疗方案主要取决于雌激素（雌激素受体α）、孕激素（孕激素受体）和人表皮生长因子[人表皮生长因子受体2（HER2）]的受体状态。这些受体中一种或多种的存在表明针对这些途径的治疗可能有效，而所有这些受体均不存在，或者在HER2的情况下缺乏过表达，即所谓的三阴性乳腺癌（TNBC），则表明需要采用毒性更大的化疗。为了开发针对TNBC的靶向治疗方法，有必要区分特定的TNBC亚型。已确定表达雄激素受体（AR）的TNBC子集表达与管腔亚型一致的基因，因此可能适合针对AR本身或管腔亚型典型的其他途径的治疗。最近对乳腺癌内AR信号通路的研究导致AR成为乳腺癌治疗的重要靶点，目前有几项临床试验正在进行。缺乏AR的TNBC亚类，我们称之为四阴性乳腺癌（QNBC），目前缺乏明确的可靶向途径。与AR阳性TNBC不同，QNBC主要表现为基底样分子亚型。几种亚型和相关途径蛋白在QNBC中优先表达，可能作为有效的治疗靶点，如ACSL4、SKP2和EGFR。ACSL4的表达已被证明与激素/生长因子受体的表达呈负相关，因此可能作为QNBC的生物标志物以及治疗靶点。在以下综述中，我们总结了目前为开发TNBC和QNBC化疗替代方案所做的一些努力。
