Predicting and preventing melanoma invasiveness: advances in clarifying E2F1 function

Abstract

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.

Keywords::

• antimetastatic therapy
• cancer signaling pathways
• E2F transcription factor
• epidermal growth factor receptor
• invasiveness
• malignant melanoma
• metastasis
• RNA interference
• targeted cancer therapeutics

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.