Pathogenesis and treatment of prostate cancer bone metastases: Targeting the lethal phenotype
Pathogenesis and treatment of prostate cancer bone metastases: Targeting the lethal phenotype
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DOI：
10.1200/jco.2005.03.0841
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发表时间：
2005-11-10
影响因子：
45.3
通讯作者：
Pienta, KJ
中科院分区：
文献类型：
--
作者：
Loberg, RD;Logothetis, CJ;Pienta, KJ
传统上，前列腺癌治疗以及所有癌症治疗都被设计为通过各种激素和化疗药物直接靶向肿瘤细胞。最近，人们认识到癌细胞存在于复杂的微环境中，这对癌细胞的致瘤和转移潜力是必不可少的，这一认识开始重新定义癌症治疗的范式。前列腺癌细胞向骨骼转移的倾向导致了针对癌细胞和骨骼微环境的新疗法的设计。骨骼中的肿瘤细胞与细胞外基质、基质细胞、成骨细胞、破骨细胞和内皮细胞相互作用，促进肿瘤细胞的存活和增殖，导致致命的表型，包括晚期前列腺癌患者的发病率和死亡率增加。针对这些复杂的肿瘤细胞与微环境的相互作用，以及对转移发展至关重要的其他细胞的信号转导通路，包括破骨细胞、成骨细胞和骨微环境的内皮细胞，正在开发几种策略。目前和新的转移性前列腺癌治疗方法将包括针对肿瘤细胞和肿瘤微环境的多靶点方法。在这里，我们回顾了目前针对前列腺癌-骨微环境的治疗策略，以及几种正在开发中的晚期前列腺癌的单药和多药靶向治疗方法。
Traditionally, prostate cancer treatment, as well as all cancer treatment, has been designed to target the tumor cell directly via various hormonal and chemotherapeutic agents. Recently, the realization that cancer cells exist in complex microenvironments that are essential for the tumorigenic and metastatic potential of the cancer cells is starting the redefine the paradigm for cancer therapy. The propensity of prostate cancer cells to metastasize to bone is leading to the design of novel therapies targeting both the cancer cell as well as the bone microenvironment. Tumor cells in the bone interact with the extracellular matrix, stromal cells, osteoblasts, osteoclasts, and endothelial cells to promote tumor-cell survival and proliferation leading to a lethal phenotype that includes increased morbidity and mortality for patients with advanced prostate cancer. Several strategies are being developed that target these complex tumor cell-microenvironment interactions and target the signal transduction pathways of other cells important to the development of metastases, including the osteoclasts, osteoblasts, and endothelial cells of the bone microenvironment. Current and new therapies in metastatic prostate cancer will comprise a multitargeted approach aimed at both the tumor cell and the tumor microenvironment. Here, we review the current therapeutic strategies for targeting the prostate cancer-bone microenvironment and several single- and multiagent targeted approaches to the treatment of advanced prostate cancer that are under development.