Antibody-Mediated Targeting of Alpha PDGF Receptor to Inhibit the Progression of Skeletal Micro-Metastases
Annual rept. 21 Sep 2010-20 Sep 2011
DREXEL UNIV COLL OF MEDICINE PHILADELPHIA PA
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In this second year of funding we have shown that a We have established the time frame during which PDGFR support the survival and progression of PCa cells disseminated to the skeleton. The results deriving from our pre-clinical animal model of metastasis indicate that this receptor is of paramount importance during the initial phases of bone colonization. This information presents high value for the stratification of patients to be included in phase-III clinical trials for the antibody IMC- 3G3 Olaratumab. Thus monoclonal, fully human antibody is directed to target PDGFR and being currently evaluated in phase-II trials for a variety of solid tumors, including PCa. b We have identified a new 3-gene expression signature correlated with the ability of PCa cells to colonize the skeleton in animals. The implications for human pathology need to be fully evaluated however, the evidence accumulated in our pre-clinical model is compelling. Interestingly, all the encoded protein products are soluble and secreted proteins. This seems to indicate that PCa cells with metastatic abilities modify the bone microenvironment in a paracrine fashion and that surrounding stromal cells may reciprocate by producing survival and growth factors. If this model is confirmed, our results may help identifying novel molecular targets for anti-metastatic therapies.
- Medicine and Medical Research