The prognosis for patients afflicted with melanoma is directly related to the depth of invasion of the primary lesion at the time of diagnosis. Thus, when detected at an early stage, the patient is often cured by a wide and deep excision of the melanoma. However, once a primary lesion metastasizes, the prognosis is grave because conventional chemotherapy and/or radiation treatment do not reliably affect the course of this disease. To implement strategies that can interfere with progression from precursor lesions to advanced-stage melanoma, it is imperative to identify genes that govern melanocytic progression. Fibroblast growth factor receptor 1 (FGFR-1) is an important mediator of advanced-stage melanoma proliferation and as preliminary studies have indicated, possibly of melanoma progression. To specifically address whether activation or up-regulation of the FGFR-1 gene contributes to the onset of melanoma progression, we propose to develop and evaluate an FGFR-1-specific monoclonal antibody that may help identify early melanocytic lesions with the capacity for progression to advanced-stage melanoma. Secondly, we would like to investigate whether injection of this antibody into human melanomas grown as subcutaneous tumors in nude mice, can impair tumor growth.
Availability of an FGFR-1-specific monoclonal antibody is expected to be of great importance in the histopathologic diagnosis of melanoma precursor lesions. Furthermore, in an adjuvant setting of melanoma it may in combination with other treatment modalities, help reduce tumor burden.
