Matthews Shawna B, Sartorius Carol A
Department of Pathology, University of Colorado Anschutz Medical Campus, 12801 E 17th Ave MS8104, Aurora, CO, 80045, USA.
Horm Cancer. 2017 Feb;8(1):4-15. doi: 10.1007/s12672-016-0275-0. Epub 2016 Oct 28.
The vast majority of breast cancers are positive for estrogen receptor (ER) and depend on estrogens for growth. These tumors are treated with a variety of ER-targeted endocrine therapies, although eventual resistance remains a major clinical problem. Other steroid hormone receptors such as progesterone receptor (PR) and androgen receptor (AR) are emerging as additional prospective targets in breast cancer. The fundamental mechanism of action of these steroid receptors in gene regulation has been defined mainly by several breast cancer cell lines that were established in the late 1970s. More recently, breast cancer patient-derived xenografts (PDX) have been developed by multiple groups at institutions in several countries. These new models capture the large degree of heterogeneity between patients and within tumors and promise to advance our understanding of steroid hormone receptor positive breast cancer and endocrine resistance. Unfortunately, steroid hormone receptor positive breast cancers are much more difficult than their receptor negative counterparts to establish into sustainable PDX. Herein we discuss the derivation of steroid hormone receptor positive breast cancer PDX, several pitfalls in their genesis, and their utility in preclinical and translational steroid hormone receptor research.
绝大多数乳腺癌雌激素受体（ER）呈阳性，其生长依赖雌激素。这些肿瘤采用多种针对ER的内分泌疗法进行治疗，尽管最终耐药仍是一个主要的临床问题。其他类固醇激素受体，如孕激素受体（PR）和雄激素受体（AR），正成为乳腺癌中额外的潜在靶点。这些类固醇受体在基因调控中的基本作用机制主要由20世纪70年代末建立的几种乳腺癌细胞系所确定。最近，多个国家的机构中的多个团队开发了乳腺癌患者来源的异种移植模型（PDX）。这些新模型体现了患者之间以及肿瘤内部的高度异质性，并有望增进我们对类固醇激素受体阳性乳腺癌和内分泌耐药性的理解。不幸的是，与受体阴性的乳腺癌相比，类固醇激素受体阳性的乳腺癌要建立可持续的PDX困难得多。在此，我们讨论类固醇激素受体阳性乳腺癌PDX的衍生、其产生过程中的几个陷阱以及它们在临床前和转化性类固醇激素受体研究中的效用。
