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Fatemeh Khatami,1 Bagher Larijani,2,3 Shekoufeh Nikfar,3,4 Mandana Hasanzad,3,5 Kiarad Fendereski,6 Seyed Mohammad Tavangar1,7 1Chronic Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran; 2Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran; 3Personalized Medicine Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran; 4Department of Pharmacoeconomics and Pharmaceutical Administration, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; 5Medical Genomics Research Center, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; 6Pediateric Urology and Regenerative Medicine Research Center, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran; 7Department of Pathology, Dr. Shariati Hospital, Tehran University of Medical Sciences, Tehran, IranCorrespondence: Seyed Mohammad TavangarDepartment of Pathology, Dr. Shariati Hospital, Tehran University of Medical Sciences, Jalale Ale Ahmad Ave, Tehran, IranTel +98 218 490 2187Fax +98 218 863 3078Email Tavangar@ams.ac.irAbstract: Thyroid cancer is one of the most common endocrine malignancies, with increasing incidence all over the world. In spite of good prognosis for differentiated thyroid carcinoma, for an unknown reason, about 5–10% of the patients, the cancer will show aggressive behavior, develop metastasis, and be refractory to treatment strategies like radioactive iodine. Regarding the genetic information, each thyroid cancer patient can be considered as an individual unique one, with unique genetic information. Contrary to standard chemotherapy drugs, target therapy components aim at one or more definite molecular pathway on cancer cells, so their selection is underlying patient’s genetic information. Nowadays, several mutations and rearrangements including BRAF, VEGF receptors, RET, and RET/PTC, KDR, KIT, PDGFRA, CD274, and JAK2 are taken into account for the therapeutic components like larotrectinib (TRK inhibitor), vemurafenib, sunitinib, sorafenib, selumetinib, and axitinib. With the new concept of personalized treatment of thyroid cancer diagnoses, planning treatment, finding out how well treatment will work, and estimating a prognosis has changed for the better over the last decade.Keywords: personalized medicine, target therapy, molecular testing

Fatemeh Khatami,1 Moloud Payab,2 Masoumeh Sarvari,3 Kambiz Gilany,3–5 Bagher Larijani,6 Babak Arjmand,7 Seyed Mohammad Tavangar1,8 1Chronic Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran; 2Obesity and Eating Habits Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran; 3Metabolomics and Genomics Research Center, Endocrinology and Metabolomics Molecular Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran; 4Reproductive Biotechnology Research Center, Avicenna Research Institute, Academic Center for Education, Culture and Research (ACECR), Tehran, Iran; 5Integrative Oncology Department, Breast Cancer Research Center, Motamed Cancer Institute, Acercr, Tehran, Iran; 6Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran; 7Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran; 8Department of Pathology, Dr. Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran Introduction: Thyroid cancer (TC) is an important common endocrine malignancy, and its incidence has increased in the past decades. The current TC diagnosis and classification tools are fine-needle aspiration (FNA) and histological examination following thyroidectomy. The metabolite profile alterations of thyroid cells (oncometabolites) can be considered for current TC diagnosis and management protocols.Methods: This systematic review focuses on metabolite alterations within the plasma, FNA specimens, and tissue of malignant TC contrary to benign, goiter, or healthy TC samples. A systematic search of MEDLINE (PubMed), Scopus, Embase, and Web of Science databases was conducted, and the final 31 studies investigating metabolite biomarkers of TC were included.Results: A total of 15 targeted studies and 16 untargeted studies revealed several potential metabolite signatures of TC such as glucose, fructose, galactose, mannose, 2-keto-d-gluconic acid and rhamnose, malonic acid and inosine, cholesterol and arachidonic acid, glycosylation (immunoglobulin G [IgG] Fc-glycosylation), outer mitochondrial membrane 20 (TOMM20), monocarboxylate transporter 4 (MCT4), choline, choline derivatives, myo-/scyllo-inositol, lactate, fatty acids, several amino acids, cell membrane phospholipids, estrogen metabolites such as 16 alpha-OH E1/2-OH E1 and catechol estrogens (2-OH E1), and purine and pyrimidine metabolites, which were suggested as the TC oncometabolite.Conclusion: Citrate was suggested as the first most significant biomarker and lactate as the second one. Further research is needed to confirm these biomarkers as the TC diagnostic oncometabolite. Keywords: biomarkers, oncometabolites, thyroid cancer, TC, systematic review