Models and Mechanisms of Acquired Antihormone Resistance in Breast Cancer: Significant Clinical Progress Despite Limitations.
Models and Mechanisms of Acquired Antihormone Resistance in Breast Cancer: Significant Clinical Progress Despite Limitations.
复制标题
DOI：
10.1515/hmbci-2011-0004
复制
发表时间：
2012-02
影响因子：
1
通讯作者：
Jordan VC
中科院分区：
文献类型：
--
作者：
Sweeney EE;McDaniel RE;Maximov PY;Fan P;Jordan VC
乳腺癌治疗和预防的转化性研究依赖于四个MS：模型、分子和机制，以创造药物。这一针对雌激素依赖型乳腺癌的雌激素受体(ER)的过程已经在患者存活率和第一批被批准的药物(他莫昔芬和雷洛昔芬)方面取得了重大进展，以降低高风险或低风险女性的任何癌症发病率。这篇综述主要集中在少数ER阳性细胞系(MCF-7、T47D、BT474、ZR-75)的关键作用，它们继续推进我们对乳腺癌雌激素调节生物学的理解。更重要的是，模型细胞系提供了一个记录获得性抗激素耐药的发展和进化的机会。在长达十年的辅助治疗期间，对微转移疾病中发生的这种进化过程的描述在患者身上是不可能的。特别是MCF-7乳腺癌细胞系的使用，有助于发现ER阳性乳腺癌经抗激素治疗后的脆弱性。生理性雌二醇作为细胞凋亡的触发剂，导致肿瘤消退。这些在实验室中出人意料的发现已经转化为我们对雌激素在乳腺癌生与死中矛盾作用的认识的临床进展。
Translational research for the treatment and prevention of breast cancer depends upon the four Ms: models, molecules, and mechanisms in order to create medicines. The process, to target the estrogen receptor (ER) in estrogen-dependent breast cancer, has yielded significant advances in patient survivorship and the first approved medicines (tamoxifen and raloxifene) to reduce the incidence of any cancer in high- or low-risk women. This review focuses on the critical role of the few ER-positive cell lines (MCF-7, T47D, BT474, ZR-75) that continue to advance our understanding of the estrogen-regulated biology of breast cancer. More importantly, the model cell lines have provided an opportunity to document the development and evolution of acquired antihormone resistance. The description of this evolutionary process that occurs in micrometastatic disease during up to a decade of adjuvant therapy would not be possible in the patient. The use of the MCF-7 breast cancer cell line in particular has been instrumental in discovering a vulnerability of ER-positive breast cancer exhaustively treated with antihormone therapy. Physiologic estradiol acts as an apoptotic trigger to cause tumor regression. These unanticipated findings in the laboratory have translated to clinical advances in our knowledge of the paradoxical role of estrogen in the life and death of breast cancer.