Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
Curr Opin Oncol. 2012 May;24(3):205-10. doi: 10.1097/CCO.0b013e32835091bd.
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.
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-γ agonists.
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.
讨论口腔癌风险预测的最新进展，以及已在临床试验中或正在临床试验中测试的药物，以治疗口腔癌前病变（OPL）和预防口腔癌。
在涉及参加化学预防临床试验的患者的回顾性或相关性研究中，已经确定了多个 OPL 恶性转化的预测标志物，包括染色体等位基因失衡、多倍体、p53、足突蛋白、p63 或表皮生长因子受体（EGFR）过表达、EGFR 基因拷贝数增加、细胞周期蛋白 D1 多态性、特定基因表达谱和特定 DNA 甲基化谱。在这些标志物中，特定染色体位点的杂合性缺失是迄今为止描述的最一致和广泛特征的口腔癌风险的分子标志物。该生物标志物目前正在化学预防临床试验中进行前瞻性研究。已在 OPL 患者中进行或正在进行测试的药物包括类视黄醇、表皮生长因子受体抑制剂、环氧化酶-2 抑制剂、绿茶提取物和过氧化物酶体增殖物激活受体-γ 激动剂。
尽管进行了广泛的临床研究，但仍未开发出针对 OPL 患者的标准系统治疗方法。将癌症风险的生物标志物整合到使用新型药物的临床试验中，有望简化头颈部癌症化学预防研究。
