Oral cancer is known as one of the most aggressive cancers affecting people worldwide. Approximately 90 % of oral cancer cases are squamous cell carcinomas (SCCs) (Warnakulasuriya, 2009). As the sixth most common cancer in the world, over 400,000 new cases are diagnosed annually, causing over 120,000 fatalities, with numbers rising each year. The Asian population is most affected, with individuals from Sri Lanka, Indonesia, Pakistan, and India accounting for two-thirds of annual cases (Abati et al., 2020). Despite increasing progress in research, improvements have yet to be seen in recent years, with difficulty in early detection, a lack of specific disease biomarkers, highly expensive treatment alternatives, and poor prognosis.

Oral cancer is often diagnosed at a late stage, which lowers cure rates to 30 % with less than 50 % survival at 5 years (Rivera, 2015). Patients who receive treatment see their quality of life severely impacted. Surgical resections result in permanent disfigurements and physical damage with significant functional and aesthetic complications, causing difficulties to several critical functions of the head and neck (Retzbach et al., 2018, Wong and Wiesenfeld, 2018). The toxicities associated with standard chemotherapeutic agents, to which OSCC is notoriously resistant, put a patient at additional risk of life-threatening complications (Mason et al., 2016, Ochoa-Alvarez et al., 2015). As prognosis of OSCC remains poor, the search for novel treatment methods becomes a pressing demand. The development of new therapeutic approaches along with strategies to facilitate the early detection or prevention of OSCC altogether would carry value in altering the landscape of oral cancer management.

Podoplanin (PDPN) is a type I transmembrane glycoprotein that has been shown to be highly expressed in oral cancer and pre-cancerous lesions. The establishment of PDPN as a biomarker and therapeutic target along with its effective inhibitors could facilitate the early detection and management of oral cancer. Nevertheless, the challenge would be to identify the most suitable candidate for clinical use. This review article explores the challenges in the management of OSCC, discusses the role of PDPN in malignant transformation, and compares the strengths & weaknesses of available candidates for PDPN inhibition.