Receptor Antagonists for Treatment of Metastatic Bone Cancer
Methods of treating secondary bone tumors with antibodies against PDGFR alpha
Skeletal metastasis occurs at a high rate in advanced prostate carcinoma and is the main cause of death for these patients. The Fatatis lab is forging new paths towards the treatment of metastatic prostate cancer by elucidating the molecular mechanisms underpinning skeletal colonization of disseminated tumor cells. Recent work has demonstrated that targeting the alpha receptor for Platelet-Derived Growth Factor (PDGFR-α) with a monoclonal antibody reduces both the number and size of skeletal metastases and increase overall survival in an animal model. This preclinical evidence provided indicates that antagonism of PDGFR-α could be applied as a method of treating prostate cancer metastasis.
Advantages
- Establishment of novel therapeutic strategies for preventing or significantly delaying the progression of skeletal metastatic lesions from prostate adenocarcinoma
- Address the needs of a very large number of metastatic patients that currently fail to receive effective, curative therapeutics for their disease
- Potential use for PDGFR-α as a biomarker for the propensity of prostate cancer to skeletal dissemination, allowing individualized assessment of patient risk
Intellectual Property and Development Status
United States Issued Patent- 8,425,911
References
Liu Q. et al. Interleukin-1β promotes skeletal colonization and progression of metastatic prostate cancer cells with neuroendocrine features. Cancer Res. 2013; 73, p. 3297-305.
Jamieson-Gladney W.L. et al. The chemokine receptor CX3CR1 is directly involved in the arrest of breast cancer cells to the skeleton. Breast Cancer Res. 2011; 13:R91.
Russell M.R. et al. Targeting the {alpha} receptor for platelet-derived growth factor as a primary or combination therapy in a preclinical model of prostate cancer skeletal metastasis. Clin Cancer Res. 2010; 16:5002-10.
Russell M.R. et al. The alpha-receptor for platelet-derived growth factor confers bone-metastatic potential to prostate cancer cells by ligand- and dimerization independent mechanisms. Cancer Res. 2010; 70:4195-203.
Jamieson W.L. et al. CX3CR1 is expressed by prostate epithelial cells and androgens regulate the levels of CX3CL1/fractalkine in the bone marrow: potential role in prostate cancer bone tropism. Cancer Res. 2008; 68:1715-22.