Thyroid cancer is the most common cancer of the endocrine system and is 
responsible for the majority of deaths from endocrine malignancies. Although a 
large proportion of thyroid cancers belong to well differentiated histologic 
subtypes, which in general show a good prognosis after surgery and radioiodine 
ablation, the treatment of radio-resistant papillary-type, of undifferentiated 
anaplastic, and of medullary-type thyroid cancers remains unsatisfactory. 
Autophagy is a vesicular process for the lysosomal degradation of protein 
aggregates and of damaged or redundant organelles. Autophagy plays an important 
role in cell homeostasis, and there is evidence that this process is 
dysregulated in cancer cells. Recent in vitro preclinical studies have indicated 
that autophagy is involved in the cytotoxic response to chemotherapeutics in 
thyroid cancer cells. Indeed, several oncogenes and oncosuppressor genes 
implicated in thyroid carcinogenesis also play a role in the regulation of 
autophagy. In addition, some epigenetic modulators involved in thyroid 
carcinogenesis also influence autophagy. In this review, we highlight the 
genetic and epigenetic factors that mechanistically link thyroid carcinogenesis 
and autophagy, thus substantiating the rationale for an autophagy-targeted 
therapy of aggressive and radio-chemo-resistant thyroid cancers.