Abstract
Well-differentiated thyroid carcinoma (DTC) is the most common endocrine malignancy that has an excellent prognosis with a 5-year survival rate of about 98%. However, approximately 50% of the patients with DTC who present with distant metastases (advanced DTC) die from the disease within 5 years of initial diagnosis even after getting the appropriate therapy. Apart from recent advancements in chemotherapy agents, the potential role of metabolic interventions, including the use of metformin, ketogenic diet, and high-dose vitamin C in the management of advanced cancers have been investigated as a less toxic co-adjuvant therapies. The role of vitamin C has been of interest again after a preclinical mice study showed that high-dose vitamin C is selectively lethal to KRAS and BRAF mutant colorectal cancer cells by targeting the glutathione pathway. This raises the possibility of utilizing high-doses of vitamin C in the treatment of aDTC where KRAS and BRAF mutations are common. Similarly, alteration of cellular metabolism by low-carbohydrate ketogenic diets can be an important therapeutic strategy to selectively kill cancer cells that mainly survive on glycolysis. Among the potential adjuvant therapies proposed in this paper, metformin is the only agent that has shown benefit in human model of aDTC, the others have shown benefit but in preclinical/animal studies only and need to be further evaluated in large clinical trials. In conclusion, in addition to concurrent chemotherapy options, these metabolic interventions may have a great potential as co-adjuvant therapy in the management of aDTC.
Highlights
Well-differentiated thyroid carcinoma (DTC) is the most common endocrine malignancy and is classified into three major categories: papillary thyroid carcinoma, follicular thyroid carcinoma, and Hürthle cell carcinoma
DTC has an excellent prognosis with a 5-year survival rate of about 98%
Promising outcomes of vitamin C described in the management of KRAS and BRAF mutated colorectal cancer cells opened a new insight into treating aDTC
Summary
Well-differentiated thyroid carcinoma (DTC) is the most common endocrine malignancy and is classified into three major categories: papillary thyroid carcinoma, follicular thyroid carcinoma, and Hürthle cell carcinoma. DTC has an excellent prognosis with a 5-year survival rate of about 98% Despite low mortality, this disease has been treated aggressively for fear of more advanced disease and lack of effective tools for risk stratification. Given its typical protracted course and lack of effective treatments, aDTC can be considered a chronic disease, and safe and low-cost long-term interventions aiming at delaying or prevention of disease progression are more desirable. One such approach could be targeting reprogrammed glucose metabolism of advanced cancers, such as with metformin, ketogenic diet, and high-dose vitamin C [1, 2]. Metformin will be a great adjuvant anticancer agent for advanced DTC (and other cancers) because of its safety and widespread availability
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