The evolution of predictive oncology and molecular-based therapy for oral cancer prevention.
More than 300,000 new cases worldwide are being diagnosed with oral squamous cell carcinoma annually. This aggressive epithelial malignancy is associated with a high mortality and severe morbidity among the long-term survivors. The ability to intervene prior to this advanced stage may improve treatment results. This requires the early identification of molecular events that represent early phases of malignant transition, which is possible through measurement of DNA ploidy in epithelial cells of oral leukoplakia. Recently, we showed that patients with aneuploid dysplastic oral lesions had a 96% rate of oral cancer (26 of the 27 patients received the diagnosis) with a 70% rate within three years, an 81% rate of subsequent cancer (22 of 27), a 74% rate of death from cancer (21 of 27) and virtually no help from complete resection-all hallmarks of biologically aggressive cancer. Standard treatment of oral leukoplakia-a precursor lesion of oral cancer-varies from watchful waiting to complete resection. We have recently demonstrated that complete resection of aneuploid oral leukoplakia does not prevent the occurrence of clinically aggressive and highly lethal oral cancer. Oral carcinogenesis is a complex multifocal process of multiclonal field carcinogenesis and intraepithelial clonal spread. The multifocal nature of early oral carcinogenesis may hinder local treatment modalities. Inhibitors of cyclooxygenase-2 (COX-2) and epidermal growth factor receptor (EGFR), either alone or in combination, may be used for reversing or stopping the oral carcinogenesis at an early stage of disease. The failure of standard treatment to control aneuploid oral leukoplakia justifies clinical trials with new treatment modalities, such as systemic therapy with molecular targeting agents, which in patients with aggressive leukoplakia is tantamount to cancer therapy.
Sudbø
Jon
J
Department of Medical Oncology and Radiotherapy, The Norwegian Radium Hospital, University of Oslo, Oslo, Norway. jon.sudbo@rh.uio.no <jon.sudbo@rh.uio.no>
Reith
Albrecht
A
D000782:Aneuploidy; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000517:prevention & control; D004273:DNA, Neoplasm / Q000032:analysis; D006801:Humans; D007972:Leukoplakia, Oral / Q000175:diagnosis / Q000517:prevention & control; D009062:Mouth Neoplasms / Q000175:diagnosis* / Q000517:prevention & control*; D013678:Technology, Pharmaceutical
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm