Identifying Targets for Oral Cancer

Head and neck cancers account for nearly 4% of all cancers in the US.¹ The most common type is oral cancer, estimated to cause over 170,000 global deaths in 2020 alone.² These statistics highlight the urgent need for more research and better treatments.

Treatment challenges in oral cancer arise from the lack of targeted therapies, leading to systemic side effects and drug resistance. To improve clinical management, identifying molecular targets and developing effective drugs has become crucial. Research in this area holds promise for improving oral cancer treatment and transforming the lives of those affected by this disease.

Over 5000 targets associated with oral cancer were identified using Causaly, supported by 18,000+ documents. Tumor suppressor protein (p53) had the most evidence as a target for this cancer.

Known as the “guardian of the genome”, p53 regulates DNA repair and cell division, and is damaged or mutated in about half of all cancers.³ Recent findings demonstrated that p53 gene polymorphisms could be detected in both tissue and saliva samples of oral cancer patients, underscoring the potential for non-invasive saliva-based cancer screenings.⁴

Approximately 4000 potential targets have been studied preclinically, with around 1500 reported in the literature in 2022, according to Causaly. Filtering further by results sections of articles revealed over 400 targets. PRAME was identified as the target with the most evidence, and CXCL8 as a recently reported target.

The PRAME gene, also known as Preferentially Expressed Antigen in Melanoma, is involved in cell proliferation, metastasis and apoptosis. Elevated levels of PRAME have been reported in difference cancers including Hodgkin’s lymphoma and head and neck squamous cell carcinoma.⁵

Recent studies have indicated a growing interest in targeting PRAME as a potential therapeutic approach in oral cancer. A 2023 study on laryngeal squamous cell carcinoma revealed that PRAME overexpression promotes cancer cell proliferation and metastasis through the activation of the PI3K/AKT/mTOR pathway.⁶  PRAME serves as a valuable marker for identifying aggressive oral cancer cases.⁷ The results indicate the significance of PRAME in cancer progression and the need for further investigations to evaluate its efficacy.

CXCL8, also known as interleukin 8, is a pro-inflammatory chemokine which promotes tumor progression and angiogenesis. The secretion of CXCL8 has shown to enhance the migration, invasion and cisplatin resistance in oral cancer cells.⁸ Additionally, A 2023 study reported that blocking CXCL8 using monoclonal antibodies reduced the migration and invasion of oral squamous cell carcinoma.⁹ This finding suggests that manipulating chemotaxis-related pathways, such as CXCL8, could offer new avenues for improving treatment outcomes in oral cancer.

Identifying key molecular targets is vital for effective oral cancer management and therapeutic development. PRAME and CXCL8 have emerged as promising targets due to their involvement in cell division, metastasis, tumor development, and chemoresistance. However, further studies and clinical trials are needed to fully comprehend their therapeutic potential and improve patient outcomes. A deeper understanding of these promising targets is needed to fully harness their potential for effective therapies and improve treatment outcomes.

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