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Odontogenic keratocyst (OKC) is a relatively common cystic lesion occurred in the tooth-bearing areas of the jaws. This entity is thought to arise from the dental lamina or its remnant with significant growth capacity and recurrence potential. The Sonic hedgehog (SHH) signaling pathway plays a critical role in tooth development. Patched (PTCH) combines with Smoothened (SMO) to form a receptor complex for SHH ligand. Mutations in the PTCH resulting in aberrant activation of SHH signaling pathway were identified as the underlying genetic event of both sporadic and syndrome-related OKCs. We postulate that any strategy to develop antagonists of active receptor, transcriptional factors of SHH signaling pathway will be an effective treatment for OKC. These strategies include reintroducing a wild-type form of PTCH, inhibition of the SMO molecule by synthetic small antagonists and suppression of the downstream transcription factors of the SHH signaling pathway. It seems that inhibition of SMO by intracystic injection of antagonist protein of SMO is the most potential treatment choice.

Oral squamous cell carcinoma (OSCC) is the sixth most common malignancy and is a major cause of cancer morbidity and mortality worldwide. A strong association of oral cancer with high-risk HPVs infection underlines the importance of the virus in the pathogenesis of these squamous cell carcinomas. We postulate that HPV may contribute to the carcinogenesis of oral epithelial and function to stimulate transformation and proliferation of OSCC. The appropriate method, which may involve immunoprevention, immunotherapy, or immunomodulatory, needs to be developed. Not only humoral immunity, but also cellular immunity must be part of this process.

The accumulation of epidemiologic, pathologic, and animal model studies suggests that periodontal infection may be a contributing risk factor for atherosclerosis. The Toll-like receptor-4 (TLR4) signaling pathway plays an important role in the initiation and progression of periodontitis-associated atherosclerotic disease. We postulate that suppression of TLR4 signaling pathway can be an effective treatment for atherosclerosis. These strategies include prevention of ligand binding to TLR4, blocking the interactions of TLR4s and adaptors in signaling pathways, blocking the enzymes in signaling pathways, and immunostimulation with vaccine adjuvants. However, we should be aware that there may be unknown risks about the new technologies and these drugs, which may cause some unknown side effects in long-term administration.

The rationale of bacterial replacement therapy against dental caries is that relatively avirulent strains of Mutans Streptococi (MS) are most likely to occupy the same ecological niche in plaque as their more cariogenic counterparts. As known, lactate dehydrogenase (LDH) deficiency has been proposed as one aspect of a strategy to construct an effector strain because LDH-deficient mutants could affect acid production by MS so as to reduce their cariogenicity. Glucan-binding lectin (GBL) plays a very important role in the formation of dental plaque biomembrane and the adherence of S. mutans to teeth surface. The gcrR gene acts as a negative transcriptional regular of gbpc gene which encoded S. mutans GBL. We presume an LDH-deficient S. mutans mutants which harbours an insertion-deletion mutation in gcrR gene can result in overexpression of GBL and higher adherence to teeth than the wild-type S. mutans and will possess of both low-level acid production and strong colonization potential.

Adenoid cystic carcinoma of salivary glands is the epithelial tumor. There are amount of malignant occurrences of adenoid cystic carcinoma of salivary glands in the head and neck area. Cancer/testis antigens can be found in various malignant tumors, normal adult testis and occasionally placenta, but not in the other normal adult tissues. This characteristic makes Cancer/testis antigens as potential markers to be applied in immunotherapeutic strategies against cancer. It has been shown that in different tumors, the expression of certain Cancer/testis antigens is activated treated with 5-aza-CdR via the demethylation of their promoter CpG islands. It is logical that multiple Cancer/testis antigens may correlate with the clinicopathologic factors of adenoid cystic carcinoma of salivary glands and be the potential markers of prognosis treated with 5-aza-CdR. So the hypothesis will provide the new direction that we can use Cancer/testis antigens as candidate antigens for adenoid cystic carcinoma of salivary glands immunotherapy due to the high expression rate activated with 5-aza-CdR.