Targeting the BMP pathway in metastatic cancer

 描述(由申请人提供)： 癌症和随后的转移性疾病仍然是死亡的一个重要来源。治疗和结果在很大程度上取决于癌症是否已经扩散或转移，一旦癌症不再局限于局部，患者的预后就很差。一旦患者发生转移，我们几乎没有治疗机会，通常会导致姑息治疗。该项目旨在研究转移性前列腺癌中的骨形态发生蛋白(BMP)途径，初步数据表明，BMP可能是治疗的靶点，并可能彻底改变转移性疾病的治疗方法。这一建议集中在三个关键领域：1)骨转移，它可能依赖于BMP信号的持续存在。2)髓系细胞抑制抗肿瘤免疫反应，这可能是BMP依赖性的。3)通过体内靶向髓系免疫抑制细胞BMP信号，恢复适应性免疫系统杀伤肿瘤细胞。退伍军人管理局科学家最初为心血管药物开发的小分子BMP拮抗剂的使用，可能会成为对抗转移性癌症的新疗法。

 DESCRIPTION (provided by applicant): Cancer and subsequent metastatic disease continue to be a significant source of mortality. Treatment and outcome are largely determined by whether the cancer has disseminated or metastasized, and once the cancer is no longer locally confined, patient prognosis is poor. We have few treatment opportunities for patients once they have metastases, typically resulting in palliative care. This project aims to study the Bone Morphogenetic Protein (BMP) pathway in metastatic prostate cancers, which preliminary data indicates may be a target for therapy and could potentially revolutionize the management of metastatic disease. This proposal focuses on three key areas: 1) Skeletal metastases, which may be dependent upon BMP signaling to persist. 2) Myeloid cell suppression of anti-tumor immune responses, which may be BMP dependent. 3) Restoration of the adaptive immune system to kill tumor cells through targeting in vivo the myeloid immune suppressive cells BMP signaling. Use of small molecule BMP antagonists developed by VA scientists originally for cardiovascular medicine may hold promise as novel treatments in the fight against metastatic cancers.