Poorly Differentiated and Anaplastic Thyroid Cancer: Insights into Genomics, Microenvironment and New Drugs

Abstract

PDTC and ATC present median overall survival of 6 years and 6 months, respectively. In spite of their rarity, patients with PDTC and ATC represent a significant clinical problem, because of their poor survival and the substantial inefficacy of classical therapies. We reviewed the newest findings about genetic features of PDTC and ATC, from mutations occurring in DNA to alterations in RNA. Therefore, we describe their tumor microenvironments (both immune and not-immune) and the interactions between tumor and neighboring cells. Finally, we recapitulate how this upcoming evidence are changing the treatment of PDTC and ATC.

Anaplastic Thyroid Carcinoma: An Update

“…Whether these discrepancies are linked to various sequencing techniques and/or to geographical differences in pathophysiology remains an open question. Recent results have revealed that NTRK and RET fusion can be detected in 2–3% of ATC cases [ 7 , 35 , 36 , 37 ] which is of utmost importance for the few patients who may be offered highly specific targeted therapies. If regulation of cell cycle has a crucial role in oncogenesis and particularly in ATC, protein metabolism control is also involved in tumorigenesis.…”

“…If regulation of cell cycle has a crucial role in oncogenesis and particularly in ATC, protein metabolism control is also involved in tumorigenesis. For example, about 10% of patients with ATC harbor EIF1AX mutations, which has recently been involved in deregulating protein synthesis [ 36 ]. Interestingly, EIF1AX mutations could co-occur with RAS mutations in ATC with a positive feedback relationship between RAS and EIF1AX proteins, which reinforces c-MYC gene expression [ 28 , 38 ].…”

“…Interestingly, EIF1AX mutations could co-occur with RAS mutations in ATC with a positive feedback relationship between RAS and EIF1AX proteins, which reinforces c-MYC gene expression [ 28 , 38 ]. Molecular alteration of the Wnt signaling pathway could also be observed, notably with β-catenin gene ( CTNNB1 ), AXIN1 and APC mutations [ 36 ]. Although increased levels of cytoplasmic β-catenin are observed in most thyroid cancer cells, mutations of β-catenin that lead to nuclear localization of the protein are limited to PDTC and ATC, suggesting a role in tumor progression [ 39 ].…”

Nutrition in Advanced Thyroid Cancer Patients

“…Other histological types are much less common but have a more aggressive nature, like Hürthle cell carcinoma and poorly differentiated carcinoma (PDTC), which account for 2% and 5% of TC, respectively [ 3 ]. Compared to DTC, PDTC is characterized by a higher risk of persistence/recurrence (both at local and distant sites), and by a higher mortality rate with a median survival rate of 6 years [ 5 , 6 ]. Anaplastic thyroid carcinoma (ATC), the most aggressive among thyroid tumors, represents only 1% of all TCs, but accounts for the majority of all TC deaths and has a median survival of 6 months [ 6 ].…”

“…Compared to DTC, PDTC is characterized by a higher risk of persistence/recurrence (both at local and distant sites), and by a higher mortality rate with a median survival rate of 6 years [ 5 , 6 ]. Anaplastic thyroid carcinoma (ATC), the most aggressive among thyroid tumors, represents only 1% of all TCs, but accounts for the majority of all TC deaths and has a median survival of 6 months [ 6 ]. This tumor is unable to take up RAI and has had no chance of cure so far [ 6 , 7 ].…”