Carcinoembryonic Antigen (CEA) as a Therapeutic Target in Medullary Thyroid Cancer (MTC)

Background/Objectives: Medullary thyroid cancer (MTC) is a rare but aggressive neuroendocrine malignancy arising from parafollicular C cells. Despite its low incidence, MTC has historically been estimated to account for 13.4% of thyroid cancer-related deaths. Survival outcomes remain limited in advanced disease, with a historical cohort reporting a 10-year survival of 21% for stage IV MTC, supporting the need for novel therapeutic approaches. Carcinoembryonic antigen (CEA), a fetal glycoprotein minimally expressed in normal adult tissues, is elevated in various malignancies and plays an established role in carcinogenesis, metastasis, and therapy resistance. In MTC, CEA is produced by neoplastic C cells alongside calcitonin, and both serum and tumor-associated CEA levels are markedly elevated relative to healthy tissue. More than half of MTC patients demonstrate elevated CEA, and intense CEA immunohistochemical staining correlates with aggressive, disseminated disease, highlighting its potential utility as both a biomarker and investigational therapeutic target in the disease. For MTC, surgery is the mainstay for locoregional disease with the intent for complete surgical resection when possible. Systemic therapy is generally reserved for structurally progressive, unresectable, symptomatic, or threatening advanced disease, with selective RET inhibitors used in RET-mutant disease and multi-kinase TKIs as additional treatment options. Although TKIs have improved progression-free survival, treatment can be limited by toxicities and the development of resistance over time. These limitations underscore the need for novel therapeutic strategies that can achieve more durable disease control and improve overall survival. Given its strong association with tumor burden, disease progression, and aggressive pathology, CEA represents a promising investigational target for therapeutic exploration in MTC. Methods: A narrative literature review was performed to evaluate carcinoembryonic antigen (CEA) as a therapeutic target and biomarker in medullary thyroid cancer (MTC). Searches were conducted in 2025 and 2026 using PubMed/MEDLINE, Embase, Cochrane Library, Scopus, Web of Science, and ClinicalTrials.gov. Conclusions: The current literature supports further investigation of CEA targeting as a therapeutic strategy in MTC. However, CEA is not yet a clinically validated therapeutic target and clinical trial data remain limited.