Introduction: Oral squamous cell carcinoma (OSCC) ranks among the top 10 leading causes of cancer worldwide, with 5-year survival rate of about 50%, high lymph node metastasis, and relapse rates. The OSCC diagnosis, prognosis, and treatment are mostly based on the clinical TNM classification. There is an urgent need for the discovery of biomarkers and therapeutic targets to assist in the clinical decision-making process.Areas covered: We summarize proteomic studies of the OSCC tumor, immune microenvironment, potential liquid biopsy sites, and post-translational modifications trying to retrieve information in the discovery and verification or (pre)validation phases. The search strategy was based on the combination of MeSH terms and expert refinement.Expert opinion: Untargeted combined with targeted proteomics are strategies that provide reliable and reproducible quantitation of proteins and are the methods of choice of many groups worldwide. Undoubtedly, proteomics has been contributing to the understanding of OSCC progression and uncovers potential candidates as biomarker or therapeutic targets. Nevertheless, none of these targets are available in the clinical practice yet. The scientific community needs to overcome the limitations by investing in robust experimental designs to strengthen the value of the findings, leveraging the translation of knowledge, and further supporting clinical decisions.
Keywords: Proteomics; biomarkers; liquid biopsies; mass spectrometry; oral cancer; peptidomics; post-translational modifications; tumor microenvironment.