Repositioning therapy for thyroid cancer: new insights on established medications Yevgeniya Kushchayeva 1 , Kirk Jensen, Kenneth D Burman 1 and Vasyl Vasko Department of Pediatrics, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, Maryland 20814-4712, USA 1 Division of Endocrinology, Department of Medicine, Washington Hospital Center, 110 Irving Street Northwest, Washington, District of Columbia, USA Correspondence should be addressed to V Vasko Email vasyl.vasko@usuhs.edu Abstract Repositioning of established non-cancer pharmacotherapeutic agents with well-known activity and side-effect profiles is a promising avenue for the development of new treatment modalities for multiple cancer types. We have analyzed some of the medications with mechanism of action that may have relevance to thyroid cancer (TC). Experimental in vitro and in vivo evidences, as well as results of clinical studies, have indicated that molecular targets for medications currently available for the treatment of mood disorders, sexually transmitted diseases, metabolic disorders, and diabetes may be active and relevant in TC. For instance, the derivatives of cannabis and an anti-diabetic agent, metformin, both are able to inhibit ERK, which is commonly activated in TC cells. We present here several examples of well-known medications that have the potential to become new therapeutics for patients with TC. Repositioning of established medications for the treatment of TC could broaden the scope of current therapeutic strategies. These diverse treatment choices could allow physicians to provide an individualized approach to optimize treatment for patients with TC. Key Words " repositioning therapy " thyroid cancer " cannabinoids " valproic acid " lithium " nelfinavir " chloroquine " arsenic " statins " metformin Endocrine-Related Cancer (2014) 21, R183–R194 Introduction Thyroid cancer (TC) is the most common endocrine malignancy. An estimated, 60 220 new cases of TC and 1850 TC-related deaths are expected in 2013 in the USA. Survival of patients with TC depends upon multiple factors, including cancer type and stage. The 5-year survival rate is more than 90% in patients with localized papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC), and only 53.9% in patients with distant metastases (Schlumberger 1998). The prognosis for patients with medullary thyroid cancer (MTC) depends on the stage of tumor progression at the time of diagnosis, with a mean 10-year survival rate of 100, 93, 71, and 21% for stages I, II, III, and IV respectively (Modigliani et al. 1998). An increasing number of phase I and II studies have been conducted to evaluate the efficacy of new molecular targeted drugs, such as tyrosine kinase inhibitors, inhibitors of angiogenesis, radio-immunotherapy, and re-differentiation drugs (Lanzi et al. 2009, Liebner & Shah 2011). Several targeted therapies have shown promising biochemical response and have resulted in the inhibition of targeted signaling pathways in TC cells. Most of these therapeutic modalities, however, were associated frequently with high toxicity rates. Endocrine-Related Cancer Review Y Kushchayeva et al. Repositioning therapy for thyroid cancer 21 :3 R183–R194 http://erc.endocrinology-journals.org q 2014 Society for Endocrinology DOI: 10.1530/ERC-13-0473 Printed in Great Britain Published by Bioscientifica Ltd. Downloaded from Bioscientifica.com at 05/05/2021 03:51:52AM via free access