Researchers from the Maurice Wilkins Centre and Auckland University of Technology have reviewed evidence suggesting that cannabidiol (CBD) could improve outcomes for patients with oral squamous cell carcinoma (OSCC) when paired with epidermal growth factor receptor–tyrosine kinase inhibitors (EGFR-TKIs).
Researchers note that OSCC, which represents the vast majority of head and neck squamous cell carcinomas (HNSCC), remains difficult to treat, with advanced cases showing five-year survival rates below 30%. Despite progress in surgery, radiation, chemotherapy, and immunotherapy, resistance and relapse remain major challenges.
EGFR-TKIs such as gefitinib and afatinib have emerged as promising targeted therapies, but their benefits in HNSCC have been modest compared to cancers like non-small cell lung cancer. Many OSCC tumors display high EGFR expression, yet responses to EGFR inhibitors are often limited due to mutations in downstream pathways such as PI3K, which allow cancer cells to keep proliferating even when EGFR is blocked.
The study states that CBD, a non-psychoactive compound derived from cannabis, has been shown in preclinical studies to inhibit PI3K/Akt signaling, induce apoptosis and autophagy, and reduce angiogenesis. This makes it a potential complement to EGFR-TKIs. The review notes that CBD could not only target EGFR-related growth signals but also act on other receptor tyrosine kinases, such as HER2, VEGFR, and PDGFR, all of which play roles in tumor growth, angiogenesis, and metastasis.
Importantly, CBD has demonstrated the ability to overcome drug resistance in other cancers, including cisplatin-resistant lung cancer, suggesting similar benefits could extend to oral cancer.
Beyond its anticancer effects, CBD may also improve quality of life for patients. It is already used to manage chemotherapy-related nausea, pain, and fatigue, and it possesses neuroprotective, anti-inflammatory, and anxiolytic properties. Incorporating CBD into treatment regimens could therefore ease the burden of therapy-related side effects while potentially enhancing overall efficacy.
The authors highlight evidence that CBD can directly bind to the EGFR tyrosine kinase domain and inhibit its activation, though at lower potency than drugs like afatinib. When combined with TKIs, however, CBD has shown synergistic effects in laboratory studies, enhancing tumor cell death while reducing drug toxicity. This interaction underscores the promise of a dual approach targeting EGFR through both established TKIs and CBD.
While preclinical findings are encouraging, the researchers stress that no clinical data yet confirm CBD’s effectiveness as an adjunct to EGFR-targeted therapies in OSCC or HNSCC. Rigorous studies, including animal models and clinical trials, will be needed to determine safety, dosing, and therapeutic benefit. Nonetheless, the review frames CBD as a compelling candidate for integration into future cancer treatment strategies—particularly for patients with resistant or aggressive oral cancers where current therapies fall short.
In conclusion, the review underscores that combining CBD with EGFR inhibitors could represent a new direction in oral cancer therapy, with the potential to turn a modestly effective targeted therapy into a more powerful option. By addressing both molecular resistance pathways and treatment side effects, this approach could improve survival rates and quality of life for patients battling one of the world’s most common and challenging cancers.
The researchers published their findings in the journal Current Issues in Molecular Biology
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