Novel therapeutic clues in thyroid carcinomas: The role of targeting cancer stem cells

Abstract

Thyroid carcinomas (TCs), the most common endocrine tumors, represent the eighth most common cancer diagnosed worldwide in both women and men. To treat these malignancies, several drugs are now available and a number of novel ones have been enrolling in clinical trials, addressing both oncogenic pathways in cancer cells and angiogenic pathways in tumor endothelial cells. However, their use is not devoid of serious toxicities and their efficacy is limited, being dependent on carcinoma typology and the occurrence of acquired resistance. Accordingly, it is time to recast therapeutic strategies against these types of tumors to get to newer and fully effective drugs. In this perspective, latest findings demonstrate that cancer stem cells (CSCs) represent a challenging target to strike. They possess core traits of self-renewal and differentiation, being resistant to the effects of chemotherapy and radiation and playing a key role in mediating metastasis. Therefore, basic molecular elements sustaining both development of thyroid cancer stem cells and their residence in the stemness condition represent a set of innovative and still unexplored targets to address. In this review, a thorough literature survey has been accomplished, to take stock of mechanisms governing thyroid carcinomas and to point out both their currently available treatments and the novel forthcoming ones. Pubmed, Scifinder and ClinicalTrials.gov were exploited as research applications and registry database, respectively. Original articles, reviews, and editorials published within the last ten years, as well as open clinical investigations in the field, were analyzed to suggest new exciting therapeutic opportunities for people affected by TCs.

Novel Therapies Against Aggressive Differentiated Thyroid Carcinomas

“…Efficacy of tyrosine kinase inhibitors in TC Tyrosine kinase inhibitors (TKIs) are increasingly being used in advanced and RAIRTC, for which the therapeutic options have been limited for decades. Two TKIs are currently approved for advanced TC, others being used off-label based on the results of Phase II trials [27,29] and some are being studied in Phase I, II or III [27,[33][34].…”

“…Details about the name of the drugs, phase of the study, primary outcomes, patients enrolled, time of start and estimated time of completion may be seen in Tables 3 & 4 [27,[46][47].…”

“…Vemurafenib and dabrafenib are small inhibitors highly selective to the BRAF-V600E mutations, which are being studied in Phase II trials [27][28][29][30].…”

“…Dabrafenib associated with trametinib revealed promising results in recurrent TC [27,28]. The most common AEs with these drugs are dermatological, gastrointestinal and constitutional [28,30].…”

“…Trametinib is under evaluation in a Phase II study to test tumoral iodine reincorporation in advanced TC [27].…”