Autophagy and endocrine resistance in breast cancer.
Autophagy and endocrine resistance in breast cancer.
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DOI：
10.1586/era.11.111
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发表时间：
2011-08
影响因子：
3.3
通讯作者：
Clarke R
中科院分区：
文献类型：
--
作者：
Cook KL;Shajahan AN;Clarke R
美国癌症协会估计，仅在美国每年就有超过20万例新的乳腺癌病例被诊断出来。在这些病例中，大多数是浸润性乳腺癌，近70%是雌激素受体-α阳性。靶向雌激素受体-α的治疗被广泛应用，包括选择性雌激素受体调节剂如他莫昔芬、选择性雌激素受体下调剂如氟维司群（芙仕得; FAS，ICI 182，780）或第三代芳香酶抑制剂之一，包括来曲唑或阿那曲唑。虽然这些治疗降低了乳腺癌的死亡率，但许多雌激素受体-α阳性肿瘤最终会复发，突出了内分泌治疗抵抗的临床意义。导致内分泌治疗耐药的信号转导机制尚不清楚;然而，临床前研究已经确立了自噬在获得性耐药表型中的重要作用。自噬是一种细胞在应激或营养缺乏时发生的降解过程，它试图通过分解代谢溶解聚集的蛋白质、未折叠/错误折叠的蛋白质或受损的亚细胞器来恢复代谢稳态。自噬的二重性是众所周知的，既可以是促生存的，也可以是促死亡的。然而，在乳腺癌内分泌治疗耐药的背景下，自噬的抑制可以增强先前抗雌激素耐药乳腺癌细胞的再敏感化。在这篇文章中，我们讨论了自噬在癌症和乳腺癌内分泌治疗抵抗中的复杂和偶尔矛盾的作用。
The American Cancer Society estimates that over 200,000 new breast cancer cases are diagnosed annually in the USA alone. Of these cases, the majority are invasive breast cancers and almost 70% are estrogen receptor-α positive. Therapies targeting the estrogen receptor-α are widely applied and include selective estrogen receptor modulators such as tamoxifen, a selective estrogen receptor downregulator such as Fulvestrant (Faslodex; FAS, ICI 182,780), or one of the third-generation aromatase inhibitors including letrozole or anastrozole. While these treatments reduce breast cancer mortality, many estrogen receptor-α-positive tumors eventually recur, highlighting the clinical significance of endocrine therapy resistance. The signaling leading to endocrine therapy resistance is poorly understood; however, preclinical studies have established an important role for autophagy in the acquired resistance phenotype. Autophagy is a cellular degradation process initiated in response to stress or nutrient deprivation, which attempts to restore metabolic homeostasis through the catabolic lysis of aggregated proteins, unfolded/misfolded proteins or damaged subcellular organelles. The duality of autophagy, which can be either pro-survival or pro-death, is well known. However, in the context of endocrine therapy resistance in breast cancer, the inhibition of autophagy can potentiate resensitization of previously antiestrogen resistant breast cancer cells. In this article, we discuss the complex and occasionally contradictory roles of autophagy in cancer and in resistance to endocrine therapies in breast cancer.
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