title: Oral squamous cell carcinoma: Key clinical questions, biomarker discovery, and the role of proteomics.
abstract: BACKGROUND
  The molecular and cellular mechanisms underlying the pathogenesis of oral squamous cell carcinoma (OSCC) are relatively poorly understood and remain a subject of significant importance. However, it is well established that OSCC is associated with a variety of risk factors and notably, the high incidence rates of OSCC found in developing countries are attributable to exposure to different forms of smokeless tobacco. Despite this, the way these factors contribute to the disease pathogenesis and, in particular, the transformation from oral premalignant lesions (OPLs) to primary tumor remains unknown. Recent developments in 'omics' technologies hold promise for deciphering these mechanisms through the discovery of key molecular and cellular regulatory pathways which are involved in disease progression.
  
  
  OBJECTIVE
  The aim of this critical review is to outline, through the current etiological, epidemiological, and molecular understanding of OSCC highlighting the role of key signaling pathways in the disease, and discuss the opportunities offered by recent proteomics strategies to identify potential biomarkers and novel mechanisms for OSCC.
  
  
  CONCLUSIONS
  The recent consolidation of methods for LC-MS/MS based protein expression analysis mass spectrometry and targeted protein measurement should support the discovery of new drug targets and diagnostic methods. We suggest that such studies will be most effective if they are focused on addressing the key clinical issues in the progression and treatment of this prevalent disease.
authors.affiliation: National Center for Proteomics, University of Karachi, Karachi, Pakistan; School of Medicine and Medical Science, UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland. Electronic address: uroojmalik14@gmail.com.
authors.forename: Uzma Urooj
authors.initials: UU
authors.lastname: Malik
authors.affiliation: National Center for Proteomics, University of Karachi, Karachi, Pakistan.
authors.forename: Shamshad
authors.initials: S
authors.lastname: Zarina
authors.affiliation: School of Medicine and Medical Science, UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Pennington
mesh_terms: D014408:Biomarkers, Tumor; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000235:genetics / Q000473:pathology*; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology; D002853:Chromatography, Liquid; D018450:Disease Progression; D055088:Early Detection of Cancer; D006801:Humans; D009062:Mouth Neoplasms / Q000453:epidemiology / Q000235:genetics / Q000473:pathology*; D011230:Precancerous Conditions / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D011379:Prognosis; D040901:Proteomics; D012307:Risk Factors; D053719:Tandem Mass Spectrometry
chemical_list: D014408:Biomarkers, Tumor
keywords: Biomarker; Label-free proteomics; Multiple reaction monitoring; Oral squamous cell carcinoma; Proteomics