The Bone Microenvironment in Prostate Cancer Metastasis
The Bone Microenvironment in Prostate Cancer Metastasis
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DOI：
10.1007/978-3-030-32656-2_9
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发表时间：
2019-01-01
期刊：
影响因子：
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通讯作者：
Fatatis, Alessandro
中科院分区：
文献类型：
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作者：
DiNatale, Anthony;Fatatis, Alessandro
前列腺癌细胞倾向于种植骨骼，然后发展为临床相关的转移性肿瘤，这是公认的，也是患者发病率和死亡率的主要原因。前列腺癌的自然病史通常始于局部诊断的肿瘤，这种肿瘤可以通过手术和/或放射治疗获得成功。相当比例的患者临床治愈，但大约20-30%的患者会出现生化复发迹象，这是激素剥夺和受体拮抗剂对雄激素受体(AR)信号的抑制，在不可避免地转变为去势抵抗型前列腺癌(CRPC)之前。这一阶段与继发性肿瘤同时出现或随后迅速出现，90%以上的病例(MCRPC)累及骨骼。尽管在临床实践中推广总是不明智的，但骨转移性前列腺癌实际上是无法治愈的，这是毋庸置疑的。几十年的研究表明，骨髓提供的组织微环境与肿瘤细胞的细胞自主性一样重要，可以培养正确的条件，导致骨骼转移肿瘤的建立和发展。
The propensity of prostate cancer cells to seed the skeleton and then progress into clinically relevant metastatic tumors is widely recognized and a major cause of morbidity and mortality for patients. The natural history of prostate adenocarcinoma most frequently begins with a tumor diagnosed at a localized stage, which is successfully treated by surgical and/or radiation therapy modalities. A relevant percentage of patients are clinically cured but approximately 20–30% will develop biochemical signs of recurrence, which respond to the inhibition of androgen receptor (AR) signaling by hormone-deprivation and receptor antagonists, before the inevitable transition into castration-resistant prostate cancer (CRPC). This stage simultaneously presents with or is rapidly followed by secondary tumors, which involve the skeleton in more than 90% of cases (mCRPC). While generalization in clinical practice is always unwise, it is indisputable that bone-metastatic prostate cancer is virtually incurable. Decades of research have revealed that the tissue microenvironment provided by the bone marrow is as important as the cell-autonomous features of tumor cells in fostering the right conditions that lead to establishment and progression of metastatic tumors in the skeleton.