TOWARDS A MOLECULAR-BASIS FOR TAMOXIFEN RESISTANCE IN BREAST-CANCER
TOWARDS A MOLECULAR-BASIS FOR TAMOXIFEN RESISTANCE IN BREAST-CANCER
复制标题
DOI：
10.1093/oxfordjournals.annonc.a058251
复制
发表时间：
1992-07-01
影响因子：
50.5
通讯作者：
SMITH, IE
中科院分区：
文献类型：
--
作者：
JOHNSTON, SRD;DOWSETT, M;SMITH, IE
获得他莫昔芬耐药的乳腺癌患者可能对二线激素治疗有反应或进展为真正的内分泌耐药。这些过程的生物学基础知之甚少。他莫昔芬成功治疗后，复发时几乎没有证据表明宿主内分泌环境或药物代谢谱的变化导致了获得性耐药的发生。许多他莫昔芬耐药肿瘤仍然保留结构和功能正常的雌激素受体（ER），但将独立于雌激素生长。雌激素调节的分子事件通常支配乳腺癌敏感性乳腺癌的生长，涉及几种肽生长因子（包括TGF-α、IGF-1和TGF-β）、它们的受体和信号转导途径之间复杂的自分泌和旁分泌相互作用。现在有证据表明，许多这些促有丝分裂信号介质的组成活性可以绕过细胞对雌激素的依赖，并提供一种非依赖性生长的机制。对这些分子机制的研究可能会导致更好地了解如何克服他莫昔芬耐药的临床问题。
Breast cancer patients who acquire tamoxifen resistance may respond to second-line hormonal therapy or progress to true endocrine resistance. The biological basis for these processes are poorly understood. Following successful therapy with tamoxifen there is little evidence at relapse for change in either the host endocrine environment or drug metabolic profile to account for the development of acquired resistance. Many tamoxifen resistant tumours still retain a structurally and functionally normal oestrogen receptor (ER) and yet will grow independent of oestrogen. The oestrogen-regulated molecular events which normally govern the growth of hormone-sensitive breast cancer involve a complex autocrine and paracrine interaction between several peptide growth factors (including TGF-alpha, IGF-1 and TGF-beta), their receptors and signal transduction pathways. Evidence now exists that constitutive activity of many of these mediators of the mitogenic signal can bypass the cell's dependence on oestrogen and provide a mechanism for hormone-independent growth. Research into these molecular mechanisms may result in a better understanding of how to overcome the clinical problem of tamoxifen resistance.