Tumorigenesis and Development of Oral Cancer : Molecular Mechanism on Proliferation and Invasion

In Japan, which has entered a super-aging society, the number of oral cancer patients is expected to increase. According to the 2019 statistics by the National Cancer Center in Japan, the number of patients diagnosed with oral cancer in one year is about 22,000, and the number of patients who died is about 8,000. Thus, the prognosis of oral cancer is not good. Although the incidence of oral cancer in Japan is about 3% of all cancers, oral cancer is one of the most common cancers in the world, because of higher incidence of oral cancer in West Asian countries. As oral cancer is a marked decrease in QOL, the development of novel diagnosis for early detection and prevention of progression and treatment for reducing aesthetic and functional loss is urgently desired. In oral cancer treatment, in addition to conventional surgical and radiotherapy, anticancer drugs such as cisplatin, 5-FU, and paclitaxel are used, but their strong side effects have become a problem. In general, early cancer rarely has severe sequelae after resection, but a wider range of resection in advanced cancer affects speech and feeding. In recent years, molecular-targeted therapies have achieved remarkable results. In oral cancer, only cetuximab targeting the EGF (epidermal growth factor) receptor and immune checkpoint inhibitor, anti-human PD-L1 monoclonal antibody (nivolumab) are approved for oral cancer. There are few effective molecular-targeted therapies compared to other cancers. Recently, in addition to immunotherapy, photoimmunotherapy, superselective arterial injection chemotherapy and differentiation/apoptosis induction therapy, there have been a lot of studies on the molecular and gene therapy. For achieving the development of novel treatment, it is necessary to elucidate the molecular mechanism on the development and progression of oral cancer. The cancer cells that occur on the surface of the oral mucosa invade deeply and metastasize to cervical lymph nodes and other organs. In the process of oral cancer progression, the presence of deep invasion and metastasis is the most important prognostic factor. In this review, I introduce the molecular mechanism of proliferation and invasion in the development and progression of oral cancer including our previous findings.