Stromal Regulation of Bone Metastasis

描述（由申请人提供）：每年有800 - 900万人死于癌症，其中80%是由于癌症向远处器官的全身扩散。人们早就认识到，原发性癌症会以“特定”的偏好向远处器官扩散，而骨骼是转移性癌症最常见的器官之一。在原发肿瘤中，前列腺癌被认为是一种具有形成骨转移特异性的正异性肿瘤。超过70%的前列腺癌患者在病程或尸检中发现骨转移。前列腺癌是最常见的恶性肿瘤之一，也是男性癌症死亡的第二大原因。骨转移是前列腺癌相关死亡的主要原因，如果有的话，目前的治疗方法只有非常短期的益处。为了实现这一核心目标，Kalluri、Pandolfi和Scadden的实验室联合提出了一项重点突出的计划，以研究骨转移的生物学。TMEN网络的三个项目将产生新的转移性前列腺癌遗传小鼠模型，为前列腺癌起始细胞的生物学提供新的见解，鉴定可能的骨转移细胞起源，建立肿瘤微环境在转移性前列腺癌中的作用，重点研究前列腺和骨微环境。寻找新的治疗转移性前列腺癌的靶点，并在临床前试验中评估转移性前列腺癌的新药。该网络方案的成功完成将为转移性前列腺癌领域提供重大的新进展。

DESCRIPTION (provided by applicant): Cancer accounts for 8-9 million deaths a year, 80% of which are due to systemic spread of cancer to distant organs. It has long been recognized that primary cancers spread to distant organs with 'specific' preference, and skeleton/bone is one of the most common organs to be affected by metastatic cancer. Among primary cancers, prostate cancer is considered to be an orthotropic tumor with specific predilection to form bone metastasis. Over 70% of prostate cancer patients exhibit bone metastasis as detected during the disease course or autopsies. Prostate cancers are amongst the most commonly diagnosed malignancies and the 2nd leading cause of cancer death in men. Bone metastases are the predominant reason for prostate cancer related deaths, and current therapies have very short-term benefits, if any. To achieve the central objective, the laboratories of Kalluri, Pandolfi and Scadden have joined forces to propose a focused and cohesive plan to study the biology of bone metastasis. The three projects in this TMEN network will generate new genetic mouse models of metastatic prostate cancer, offer new insights into the biology of prostate cancer initiating cells, identify possible bone metastasis cell of origin, establish the role of tumor microenvironment in metastatic prostate cancer with specific emphasis on prostate and bone microenvironment, identify new therapeutic targets against metastatic prostate cancer and evaluate a new drugs for metastatic prostate cancer in pre-clinical trials. Successful completion of this proposed network proposal will offer significant new advances in area of metastatic prostate cancer.