Repositioning therapy for thyroid cancer: new insights on established medications

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.

The Endocannabinoid System: A Target for Cancer Treatment

“…The administration of CB2 agonist JWH133 (daily intratumoral injection of 50 µg/mL for 3 weeks) led to a considerable regression of thyroid tumors generated in nude mice by inoculation of the TC cells ARO/CB2 [106]. Endocannabinoids were effective against cancer cells with activated BRAF/ERK and/or TrkA signaling, suggesting their potential utility for the treatment of BRAF-positive papillary thyroid carcinoma (PTC) and TrkA-positive medullary thyroid cancer [107].…”

Therapeutic Cannabis and Endocannabinoid Signaling System Modulator Use in Otolaryngology Patients

“…Indications for both dronabinol and nabilone include the treatment of recalcitrant nausea and vomiting following chemotherapy in cancer patients. Dronabinol is also approved as an appetite stimulant in diseases such as AIDS which result in severe weight loss . (Table )…”

“…Although presently absent within otolaryngology literature, there is encouraging in vitro and in vivo data demonstrating significant antineoplastic potential of the ESS within a wide variety of cancer models . The ENT‐related tumors with data demonstrating the potential antineoplastic activity of cannabinoids include oropharyngeal and tongue cancer, thyroid cancer, lymphoma, basal cell, squamous cell, and melanoma . Using a mouse model, Shi et al demonstrated a strong antitumoral effect on anaplastic thyroid cancer cell lines.…”

“…Dronabinol is also approved as an appetite stimulant in diseases such as AIDS which result in severe weight loss. [77][78][79][80][81][82][83][84] (Table IV)…”

“…34,38,109,116 The ENT-related tumors with data demonstrating the potential antineoplastic activity of cannabinoids include oropharyngeal and tongue cancer, thyroid cancer, lymphoma, basal cell, squamous cell, and melanoma. 5,7,27,36,38,68,79,107,[117][118][119][120][121][122][123][124][125][126][127] Using a mouse model, Shi et al demonstrated a strong antitumoral effect on anaplastic thyroid cancer cell lines. In addition to the direct effects observed, ESS agonism was also shown to increase paclitaxel induced apoptosis by two-fold via an unknown synergistic mechanism.…”