British Association for Cancer Research/Association of Cancer Physicians/Royal Society of Medicine (Oncology Section) Joint Winter Meeting Including Symposia on 'Cutaneous Melanoma' (Incorporating the 11th Gordon Hamilton-Fairley Memorial Lecture) and 'Bladder Cancer' (Incorporating the 8th Alexander Haddow Memorial Lecture)

Abstract

Melanomas are highly variable with respect to aberrant gene expression and chromosomal lesions but share a common characteristic of an acquired independence from environmental growth factors that are needed for proliferation of normal melanocytes. This autonomy is achieved in part via the endogenous production of basic fibroblast growth factor (bFGF), which is not expressed in normal melanocytes. Other melanocyte mitogens such as acidic FGF (aFGF), K-FGF/hst, FGF-5 and FGF-6, are not expressed in melanomas, in spite of the presence of amplified K-FGF/int-2 linked genes in one out of ten melanomas. These other mitogens may however, have a role in promoting the growth of melanomas at site of metastasis since some of them are known to be produced in normal tissues. The bFGF receptor is a tyrosine protein kinase that is constitutively active in melanomas. Blocking of the tyrosine-kinase activity by antagonists, antibodies or low molecular weight inhibitors, retards melanoma growth in culture, suggesting new directions for drug design for the clinical management of metastatic melanomas.