Abstract: Methods of treating a disease or disorder characterized by cells with increased or aberrant expression of cytokeratin-8 (CK8) are disclosed. The methods typically include administering to a subject in need thereof a pharmaceutical composition including an effective amount of a CK8 inhibitor. Exemplary diseases include thyroid cancers, particularly thyroid cancers characterized by poorly differentiated or undifferentiated cells. In the most preferred embodiments the cancer is an anaplastic thyroid cancer or a poorly differentiated papillary thyroid cancer. Disclosed inhibitors include, functional nucleic acids, inhibitory anti-CK8 antibodies, inhibitory peptides, and small molecules.