Target Therapy in Thyroid Cancer: Current Challenge in Clinical Use of Tyrosine Kinase Inhibitors and Management of Side Effects

Abstract

Thyroid cancer (TC) is the most common endocrine malignancy. TC is classified as differentiated TC (DTC), which includes papillary and follicular subtypes and Hürthle cell variants, medullary TC (MTC), anaplastic TC (ATC), and poorly differentiated TC (PDTC). The standard of care in DTC consists of surgery together with radioactive iodine (131I) therapy and thyroid hormone, but patients with MTC do not benefit from 131I therapy. Patients with advanced TC resistant to 131I treatment (RAI-R) have no chance of cure, as well as patients affected by ATC and progressive MTC, in which conventional therapy plays only a palliative role, representing, until a few years ago, an urgent unmet need. In the last decade, a better understanding of molecular pathways involved in the tumorigenesis of specific histopathological subtypes of TC has led to develop tyrosine kinase inhibitors (TKIs). TKIs represent a valid treatment in progressive advanced disease and were tested in all subtypes of TC, highlighting the need to improve progression-free survival. However, treatments using these novel therapeutics are often accompanied by side effects that required optimal management to minimize their toxicities and thereby enable patients who show benefit to continue treatment and obtain maximal clinical efficacy. The goal of this overview is to provide an update on the current use of the main drugs recently studied for advanced TC and the management of the adverse events.

The prognostic and immune significance of C15orf48 in pan-cancer and its relationship with proliferation and apoptosis of thyroid carcinoma

“…Our results revealed that C15orf48 was highly expressed in PTC and could potentially serve as a biomarker for PTC. PTC is derived from the acinar cells of the thyroid gland, accounting for more than 80% of THCA, and has a relatively low malignancy, while FTC is more aggressive, with more common distant metastasis and vascular invasion (42)(43)(44). Immune scoring reveals specific immune signatures among different subtypes.…”

Clinical Implications of mTOR Expression in Papillary Thyroid Cancer—A Systematic Review

“…Still, many ongoing clinical and preclinical trials with various TKIs are being evaluated in thyroid cancer patients. Food and Drug Administration and European Medicines Agency-approved TKIs for advanced RAIR DTC are presented in Table 4 [ 67 ]. Sorafenib was approved for clinical use after a large multicenter phase III study named DECISION.…”

Rationale Efficacy and Safety Evidence of Lenvatinib and Pembrolizumab Association in Anaplastic Thyroid Carcinoma

“…Lenvatinib is an oral multi-kinase inhibitor (VEGFR1–3, PDGFR, FGFR1–4, RET, and c-KIT) [ 8 ]. Several genetic alterations have been identified in ATC molecular pathways, involving VEGFR1, VEGFR2, EGFR, PDGFRα, and KIT that lead to tumor aggressiveness and progression [ 45 , 46 ].…”

“…The most frequent adverse event (AE) in the meta-analysis was hypertension, which was effectively managed by adjusting the dose and giving antihypertensive medication. Proteinuria can be treated with lenvatinib dose reduction and timely withdrawal to prevent renal failure [ 8 , 76 ]. It is still unclear whether lenvatinib played a role in the deaths of two patients who had pneumothorax-related AE and three patients who had severe hemoptysis in the pooled meta-analysis [ 81 ].…”

“…Progression free survival (PFS) for poorly DTC (PDTC) is only 14.8 months and even shorter in ATC [ 7 ]. All patients treated with lenvatinib monotherapy ultimately develop treatment resistance and progression [ 8 ].…”