Overview on Molecular Biomarkers for Laryngeal Cancer: Looking for New Answers to an Old Problem

Simple Summary Laryngeal cancer represents one of the most common head and neck cancers worldwide. It can arise in different larynx subsites, each associated with specific clinical-pathological characteristics and treatment options. Due to the nonspecific symptoms, laryngeal cancer diagnosis often occurs in a late phase, resulting in delayed treatment and worse prognosis. Therefore, successful clinical management is strictly linked to the identification of reliable diagnostic and prognostic biomarkers. Herein, we provide an overview of the most promising molecular factors to date identified for both detection and monitoring, focusing on mutated genes, non-coding RNAs, transforming epigenetic events, inflammatory mediators, and immune-related agents. Laryngeal squamous cell cancer (LSCC) accounts for almost 25-30% of all head and neck squamous cell cancers and is clustered according to the affected districts, as this determines distinct tendency to recur and metastasize. A major role for numerous genetic alterations in driving the onset and progression of this neoplasm is emerging. However, major efforts are still required for the identification of molecular markers useful for both early diagnosis and prognostic definition of LSCC that is still characterized by significant morbidity and mortality. Non-coding RNAs appear the most promising as they circulate in all the biological fluids allowing liquid biopsy determination, as well as due to their quick and characteristic modulation useful for non-invasive detection and monitoring of cancer. Other critical aspects are related to recent progress in circulating tumor cells and DNA detection, in metastatic status and chemo-refractoriness prediction, and in the functional interaction of LSCC with chronic inflammation and innate immunity. We review all these aspects taking into account the progress of the technologies in the field of next generation sequencing.