Case report on Reversal of Field Cancerization using Nutraceuticals mapped to the aberrant pathways deciphered via NGS analysis of the neoplastic oral mucosa
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Abstract
Head and neck cancer, particularly oral cancer, presents a significant health concern in Southeast Asia with a high incidence rate, advanced stage of presentation and poor treatment outcomes. The high failure rate is due to recurrence of primary tumor and emergence of second primary tumors (SPTs) due to field cancerization. This case report focuses on a 79-year-old male with a long history of tobacco exposure, resulting in extensive field cancerization within the oral mucosa. This led to sequential development of six primaries both malignant and pre-malignant over the period of 8 years for which the patient underwent multiple surgical resections over these years. The last surgical resection specimen was subjected to Next Generation Sequencing (NGS), genetic and epigenetic alterations were identified causing dysregulation of Janus kinase/signal transducers and activators of transcription signaling pathway (JAK-STAT), Toll-like receptor signalling (TLR) and Extracellular signal regulated kinase (ERK) signalling pathways. The patient post-surgical resection is labelled as disease free; the treatment guidelines do not recommend further prescription of anticancer drugs to prevent another primary and reverse field cancerization. Also, there is lack of approved drugs targeting these pathways, a novel approach was taken using natural supplements (nutraceuticals) to modulate these dysregulated pathways. Curcumin, Epigallocatechin Gallate (EGCG) and Genistein were prescribed to downregulate TLR expression, Boswellia extracts were used to antagonize ERK activation, and Methylsulfonylmethane (MSM), Honokiol, and Berberine were employed to inhibit the JAK-STAT pathway. The patient exhibited good compliance and experienced no adverse effects. Over a span of 24 months, the patient displayed a disease-free status, and the characteristic field cancerization changes within the oral mucosa began to reverse. This unique therapeutic strategy underscores the potential of natural supplements in targeting genetic aberrations and reverting neoplastic processes, ultimately preventing the development of second primary tumors. The study highlights the significance of NGS in unravelling genomic abnormalities underlying neoplasia and supports the exploration of nutraceuticals as a viable option for correcting these aberrations. The successful application of this approach in a real-world case provides a compelling basis for further research and clinical investigation into personalized and integrative approaches for managing oral cancer and potentially other malignancies.
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