Oral premalignant lesions: any progress with systemic therapies?

Purpose of review To discuss the recent advances in oral cancer risk prediction, as well as agents that have been or are currently being tested in clinical trials, to treat oral premalignant lesions (OPLs) and prevent oral cancers. Recent findings Multiple predictive markers of OPL malignant transformation have been identified in retrospective or correlative studies involving patients enrolled in chemoprevention clinical trials, including chromosomal allelic imbalances, polysomy, p53, overexpression of podoplanin, p63 or epidermal growth factor receptor (EGFR), increased EGFR gene copy number, cyclin D1 polymorphisms, specific gene expression profiles, and specific DNA methylation profiles. Of these, loss of heterozygosity at specific chromosomal sites stands out as the most consistent and extensively characterized molecular marker of oral cancer risk described to date. This biomarker is now being prospectively integrated in chemoprevention clinical trials. Agents that have been or are currently being tested in patients with OPLs include retinoids, epidermal growth factor receptor inhibitors, cyclooxygenase-2 inhibitors, green tea extract, and peroxisome proliferator activated receptor-gamma agonists. Summary Despite extensive clinical investigations, a standard systemic therapy for patients with OPLs is yet to be developed. Integration of biomarkers of cancer risk into clinical trials using novel agents will hopefully streamline head and neck cancer chemoprevention research.