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.
Veterans disproportionately suffer from more aggressive cancer than the general population. This typically results in higher metastatic burden, limited treatment options, and high mortality. The research proposed offers the hypothesis that the Bone Morphogenetic Protein (BMP) pathway may be a target for the treatment of metastatic cancers. Soldiers work in conditions that can promote and aggravate cancers. Approximately 40,000 new cases of cancer are diagnosed yearly by the VA health systems, many of these with service related connections. Of these new cases, the five most prevalent are prostate, lung, colon, bladder and melanoma. The mortality is attributed to the metastasis and growth distant to the primary site. Data from the VA Central Cancer Registry (VACCR) suggests that 175,000 patients are treated yearly, of which a majority have greater metastasis and invasive disease. Development and implementation of new treatments for Veterans with metastatic cancer is the goal of this proposal.
