Stromal Regulation of Bone Metastasis

癌症每年造成800万至900万人死亡，其中80%是由于癌症全身扩散到远处器官。长期以来，人们已经认识到原发性癌症以“特定”偏好扩散到远处器官，并且骨骼/骨是受转移性癌症影响的最常见器官之一。在原发性癌症中，前列腺癌被认为是具有形成骨转移特异性的正交异性肿瘤。超过70%的前列腺癌患者表现出骨转移，如在疾病过程或尸检中检测到的。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，目前的治疗方法具有非常短期的益处（如果有的话）。为了实现这一核心目标，Kadhi、Pandolfi和Scadden的实验室联合起来，提出了一个有针对性的计划，以研究骨转移的生物学。TMEN网络中的三个项目将产生转移性前列腺癌的新遗传小鼠模型，为前列腺癌起始细胞的生物学提供新的见解，确定可能的骨转移细胞来源，建立肿瘤微环境在转移性前列腺癌中的作用，特别强调前列腺和骨微环境，识别针对转移性前列腺癌的新治疗靶点，并在临床前试验中评估用于转移性前列腺癌的新药。成功完成这一拟议的网络提案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.