Archive of Oncology (Jan 2005)
Aberrations of growth factors as biomarkers of cancer progression
Abstract
Cell proliferation and growth are regulated by a complex network of growth factor and growth inhibitorinitiated signal transduction pathways. The disruption of these signaling pathways through genetic, epigenetic, or somatic alterations is a major area of cancer research. Increasing evidence indicates that oncogenic activation of growth factors and their receptor proteins occur through mutations (oncoproteins) that lead to constitutive activation of the signaling pathways, thus providing the grounds for putative prognostic marker(s) and potential target(s) for treatment of various cancers. Over the past few years, the study of genomics has revealed the gene expression signatures for many malignancies. Present communication outlines literature survey on genomic molecular markers of breast, lung, and prostate cancers. Reassuringly, the dominant genomic markers of these malignancies include oncoproteins and provide a support for their clinical validity as cancer targets. More specifically, this article reviews recent advances in clinical targeting of these malignancies by two types of growth factor/receptors, namely transforming growth factor-β (TGF-β), and EGFR subfamily of tyrosine kinase receptors including ErbB2. Overexpression of these proteins has been demonstrated in patients with cancer progression and correlated with poor prognosis, increased frequency of metastasis and death. In addition, EGFR and ErbB2 inhibitors have been used in targeted therapy of lung and breast cancer, respectively. Recent investigations of lung cancer have uncovered that EGFR inhibitors have their greatest effect in patients with EGFR somatic mutations thus raising a possibility that EGFR mutations may be a molecular predictors of sensitivity to EGFR inhibitors.
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