Prognostic and Predictive Molecular Markers in Cutaneous Malignant Melanoma: The First Step Toward Personalized Medicine
Cutaneous malignant melanoma represents one of the most aggressive human cancers with high metastatic potential. Differences in the response and toxicity to current melanoma therapies among individuals are observed in nearly all-available treatment regimens. The first step toward personalized medicine is identifying a panel of biomarkers that allow classification of melanoma patients for appropriate treatment and prediction of probable response to therapy. The traditional approach to biomarker detection relied on studying a few candidate markers suspected of affecting clinical outcome. However, these studies have yielded contradictory results because of the small number of molecular determinants examined. This has been a major limitation of translational studies in malignant melanoma. Recent studies using highthroughput technologies, such as gene expression profiling and serum proteomic fingerprinting, have explored the utility of molecular markers to discriminate between clinical stages and predict disease progression in melanoma patients. This expert review highlights key approaches for the discovery and validation of biomarkers at the levels of DNA, RNA and protein. It also summarizes biomarker work performed by less invasive approaches, i.e., RT-PCR in detection of circulating melanoma cells and serum markers that may be used to monitor early response to treatment and guide the therapeutic strategy. We anticipate that pharmacogenomics will play an integral role in disease assessment, patient selection and treatment response in melanoma clinical management with the ultimate goal of individualizing treatment and improving overall survival for patients.
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Document Type: Research Article
Publication date: December 1, 2008