Review article
Medullary Thyroid Cancer – Feature Review and Update on Systemic Treatment
Nina Dabelić
; Department of Oncology and Nuclear Medicine, Sestre Milosrdnice University Hospital Centre, Zagreb, Croatia
Tomislav Jukić
; Department of Oncology and Nuclear Medicine, Sestre Milosrdnice University Hospital Centre, Zagreb, Croatia; University of Zagreb, School of Medicine
Ana Fröbe
; Department of Oncology and Nuclear Medicine, Sestre Milosrdnice University Hospital Centre, Zagreb, Croatia; University of Zagreb, School of Dental Medicine
Abstract
Medullary thyroid carcinoma (MTC) is a rare malignancy that originates from
parafollicular (C cells) of the thyroid and accounts for 2-4% of all thyroid malignancies. MTC may be
sporadic or inherited, the latter as part of the MEN 2 syndromes. Germline mutations in the RET
proto-oncogene (REarranged during Transfection) are driver mutations in hereditary MTC, whereas
somatic RET mutations and, less frequently, RAS mutations, have been described in tumor tissues of
sporadic MTC. Genetic screening for germline mutations in RET proto-oncogene identifies gene
carriers of germline mutations. That enables primary prevention (the avoidance of disease onset by
total prophylactic thyroidectomy), or at least secondary prevention (early detection) of the disease.
Radical surgery with complete tumor resection is still pivotal in attaining cure for MTC. Despite recent
advances, the treatment of advanced, metastatic, and progressive MTC remains challenging.
Metastatic MTC can have an indolent clinical course; therefore, it is necessary to assess which patient
to cure and when to initiate the treatment. Multidisciplinary boards of various specialists involved in
the diagnostics and therapy of the patients with MTC in highly specialized centers with a high volume
of patients provide optimal patient management. Multikinase inhibitors (MKI) vandetanib and
cabozantinib were approved for the treatment of progressive or symptomatic metastatic/unresectable
MTC. Although these treatments have been shown to improve progression-free survival (PFS) with
higher overall response rates (ORR) compared with placebo, no MKI has been shown to increase the
overall survival (OS) yet, except in the subgroup of patients with RETM918T-mutations on cabozantinib
therapy. As these drugs are nonselective, significant off-target toxicities may occur. Recently,
next-generation small-molecule tyrosine kinase inhibitors (TKIs) have been developed. These highly
selective RET-inhibitors are specifically designed for highly potent and selective targeting of oncogenic
RET alterations, making them promising drugs for the treatment of advanced MTC. The selective
RET-inhibitor selpercatinib has been very recently registered for the treatment of RET-mutated
thyroid cancer.
Keywords
medullary thyroid cancer; RET proto-oncogene; molecular targeted therapy; treatment; update
Hrčak ID:
247897
URI
Publication date:
1.11.2020.
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