Rationale for adjuvant fatty acid therapy to prevent radiotherapy failure and tumor recurrence during early laryngeal squamous cell carcinoma.
Information from a preceding lipid study contributed to the pathobiological assessment of laryngeal squamous cell carcinoma (LSCC). Lipid-driven signaling pathways are responsible for laryngeal carcinogenesis and immunodeficiency. The construction of fatty acid (FA) profiles for LSCC allowed the identification of FA role players. The integration of lipid and clinicomolecular information encountered in the literature, in turn, allowed the identification of biological prognostic markers to distinguish between early (less aggressive) and advanced (more aggressive) LSCCs. High arachidonic acid (AA) and cyclooxygenase (COX-2) activities are criteria for less aggressive growth, whilst low AA and COX-2 activities occur during more aggressive growth. Excessive tobacco use and environmental smoke or human papillomavirus (HPV) infection and alcohol abuse can, respectively, elicit cumulative oxidative stress and an oxidative burst or interfere with signaling pathways during essential fatty acid (EFA) metabolism, all factors and events which may cause LSCC. Research revealed that enhanced COX-2 activity and Bcl-2 expression prevent apoptosis and, hence, LSCCs become resistant to radiotherapy. It was also observed that recurrent laryngeal cancers become more aggressive after radiotherapy failure. It is predicted that manipulation of AA activity and consequently a cascade of downstream factors that include COX-2 and Bcl-2 expression responsible for LSCC may have therapeutic potential to improve radiotherapy outcome during early LSCC. Adjuvant FA therapy to improve early LSCC management by counteracting radiotherapy failure and unwanted complications for further management is proposed. FA therapeutic strategies before and during radiotherapeutic courses need to be evaluated.
Department of Otorhinolaryngology, Faculty of Health Sciences, University of the Free State, Bloemfontein 9300, South Africa. gnanll.md@mail.ouvs.ac.za
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D017209:Apoptosis; D016718:Arachidonic Acid / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism / Q000532:radiotherapy*; D017024:Chemotherapy, Adjuvant; D051546:Cyclooxygenase 2 / Q000378:metabolism; D005227:Fatty Acids / Q000627:therapeutic use*; D006801:Humans; D007822:Laryngeal Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000532:radiotherapy*; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism
D005227:Fatty Acids; D019253:Proto-Oncogene Proteins c-bcl-2; D016718:Arachidonic Acid; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human