Predicting and preventing melanoma invasiveness: advances in clarifying E2F1 function.

Malignant melanoma of the skin is one of the most aggressive human cancers with increasing incidence, despite efforts to improve primary prevention. In particular, the prognosis of patients at late stages of the disease has not significantly improved in the last three decades, because systemic therapies have proven disappointing. Thus, metastatic melanoma continues to be a daunting clinical problem. The increasingly high rates of lethal outcome associated with advanced melanoma rely on the acquisition of invasiveness, early metastatic dissemination of tumor cells from their primary sites, and generation of chemoresistance as a consequence of alteration of key molecules involved in the regulation of cell survival. Thus far, extensive studies have been conducted to understand the molecular mechanisms that drive tumor progression, but the specific requirements underlying the aggressive behavior are still widely unknown. Understanding the determinants of this process is key to unveiling its dynamics, especially those that promote invasiveness, and may open new routes for the development of therapeutic strategies that control metastatic spread, and eventually the prevention of life-threatening metastases. Here, we review recent advances on molecular aspects, particularly of E2F1 transcription factor function, in the context of patient data, and discuss the implications for targeting melanoma cells when they begin to invade and metastasize.