Oral cancer prevention and the evolution of molecular-targeted drug development.
The multifaceted rationale for molecular-targeted prevention of oral cancer is strong. Oral cancer is a major global threat to public health, causing great morbidity and mortality rates that have not improved in decades. Oral cancer development is a tobacco-related multistep and multifocal process involving field carcinogenesis and intraepithelial clonal spread. Biomarkers of genomic instability, such as aneuploidy and allelic imbalance, can accurately measure the cancer risk of oral premalignant lesions, or intraepithelial neoplasia (IEN). Retinoid-oral IEN studies (eg, of retinoic acid receptor-beta, p53, genetic instability, loss of heterozygosity, and cyclin D1) have advanced the overall understanding of the biology of intraepithelial carcinogenesis and of preventive agent molecular mechanisms and targets-important advances for monitoring preventive interventions and assessing cancer risk and pharmacogenomics. Clinical management of oral IEN varies from watchful waiting to complete resection, although complete resection does not prevent oral cancer in high-risk patients. New approaches, such as interventions with molecular-targeted agents and agent combinations in molecularly defined high-risk oral IEN patients, are urgently needed to reduce the devastating worldwide consequences of oral cancer.
Lippman
Scott M
SM
Department of Clinical Cancer Prevention, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA. slippman@mdanderson.org
Sudbø
Jon
J
Hong
Waun Ki
WK
D000782:Aneuploidy; D014408:Biomarkers, Tumor; D002278:Carcinoma in Situ / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control*; D051546:Cyclooxygenase 2; D016503:Drug Delivery Systems; D049452:Green Fluorescent Proteins / Q000037:antagonists & inhibitors; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D008565:Membrane Proteins; D009062:Mouth Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D011230:Precancerous Conditions / Q000188:drug therapy / Q000235:genetics; D011451:Prostaglandin-Endoperoxide Synthases; D018570:Risk Assessment; D012307:Risk Factors; D013678:Technology, Pharmaceutical
D014408:Biomarkers, Tumor; D007527:Isoenzymes; D008565:Membrane Proteins; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases