PDF(Pubmed)
Abstract：
Breast cancer (BC) is one of the most common and fatal malignancies among women worldwide. Circadian rhythms have emerged in recent studies as being involved in the pathogenesis of breast cancer. In this paper, we reviewed the molecular mechanisms by which the dysregulation of the circadian genes impacts the development of BC, focusing on the critical clock genes, brain and muscle ARNT-like protein 1 (BMAL1) and circadian locomotor output cycles kaput (CLOCK). We discussed how the circadian rhythm disruption (CRD) changes the tumor microenvironment (TME), immune responses, inflammation, and angiogenesis. The CRD compromises immune surveillance and features and activities of immune effectors, including CD8+ T cells and tumor-associated macrophages, that are important in an effective anti-tumor response. Meanwhile, in this review, we discuss bidirectional interactions: age and circadian rhythms, aging further increases the risk of breast cancer through reduced vasoactive intestinal polypeptide (VIP), affecting suprachiasmatic nucleus (SCN) synchronization, reduced ability to repair damaged DNA, and weakened immunity. These complex interplays open new avenues toward targeted therapies by the combination of clock drugs with chronotherapy to potentiate the immune response while reducing tumor progression for better breast cancer outcomes. This review tries to cover the broad area of emerging knowledge on the tumor-immune nexus affected by the circadian rhythm in breast cancer.
摘要：
乳腺癌（BC）是全球女性中最常见和致命的恶性肿瘤之一。最近的研究发现昼夜节律与乳腺癌的发病机理有关。在本文中,我们综述了昼夜节律基因失调影响BC发育的分子机制,专注于关键的时钟基因，脑和肌肉ARNT样蛋白1（BMAL1）和昼夜节律运动输出周期kaput（时钟）。我们讨论了昼夜节律中断（CRD）如何改变肿瘤微环境（TME），免疫反应，炎症,和血管生成。CRD损害了免疫监视以及免疫效应物的特征和活动，包括CD8+T细胞和肿瘤相关巨噬细胞，这对有效的抗肿瘤反应很重要。同时,在这次审查中,我们讨论双向相互作用：年龄和昼夜节律，衰老通过减少血管活性肠多肽（VIP）进一步增加患乳腺癌的风险，影响视交叉上核（SCN）同步，修复受损DNA的能力降低，免疫力减弱。这些复杂的相互作用通过将时钟药物与时间疗法相结合以增强免疫反应，同时减少肿瘤进展以获得更好的乳腺癌结果，从而为靶向治疗开辟了新途径。这篇综述试图涵盖有关受乳腺癌昼夜节律影响的肿瘤免疫关系的广泛知识领域。
