Braga Sofia
José de Mello Saúde, Avenida Do Forte Edifício Suécia III, Piso 2, Carnaxide, Lisbon, Portugal.
Departamento de Ciências Biomédicas e Medicina, Universidade do Algarve, Algarve, Portugal.
Methods Mol Biol. 2016;1395:105-36. doi: 10.1007/978-1-4939-3347-1_8.
Seventy five percent of all breast cancer (BC) patients express estrogen receptor (ER) but a quarter to half of patients with ER positive BC relapse on ET (endocrine therapy), tamoxifen, aromatase inhibitors (AIs), surgical castration, amongst other treatment strategies. ER positive BC at relapse loses ER expression in 20 % of cases and reduces quantitative ER expression most of the time. ER is not the only survival pathway driving ER positive BC and escape pathways intrinsic or acquired are activated during ET. This overview gives an account of ligand-independent ER activation, namely by receptor networks cross talk, and by the various genomic factors and mechanisms leading to ET response failure. Also the mechanisms of Her1 and Her2 inhibition resistance are dealt within this overview, along with the therapeutic indications and limitations of tyrosine kinase inhibitors, PARP inhibitors, PI3K/AKT/mTOR inhibitors, RAS/RAF/MEK/ERK/MAPK inhibitors, and antiangiogenic drugs. In spite of the many advances in controlling the division of BC cells and the progression of BC tumors these still remain the main cause of death among women in age range of 20-50 years requiring even more efforts in new therapeutic approaches besides the drugs within the scope of the overview.
所有乳腺癌（BC）患者中有75%表达雌激素受体（ER），但四分之一至一半的ER阳性BC患者会在接受内分泌治疗（ET）、他莫昔芬、芳香化酶抑制剂（AI）、手术去势及其他治疗策略后复发。复发时，20%的ER阳性BC病例会失去ER表达，且大多数情况下ER的定量表达会降低。ER并非驱动ER阳性BC的唯一生存途径，在ET期间，内在或获得性的逃逸途径会被激活。本综述阐述了非配体依赖性ER激活，即通过受体网络的相互作用，以及导致ET反应失败的各种基因组因素和机制。此外，本综述还探讨了Her1和Her2抑制耐药的机制，以及酪氨酸激酶抑制剂、PARP抑制剂、PI3K/AKT/mTOR抑制剂、RAS/RAF/MEK/ERK/MAPK抑制剂和抗血管生成药物的治疗适应证和局限性。尽管在控制BC细胞分裂和BC肿瘤进展方面取得了许多进展，但这些仍是20至50岁女性死亡的主要原因，除了本综述范围内的药物外，还需要在新的治疗方法上做出更多努力。
