Novel Inhibitor-Based Therapies for Thyroid Cancer-An Update.

Thyroid cancers (TCs) are the most common tumors of the endocrine system and a constant rise in the number of TC cases has been observed for the past few decades. TCs are one of the most frequent tumors in younger adults, especially in women, therefore early diagnosis and effective therapy are especially important. Ultrasonography examination followed by fine needle biopsy have become the gold standard for diagnosis of TCs, as these strategies allow for early-stage detection and aid accurate qualification for further procedures, including surgical treatment. Despite all the advancements in detection and treatment of TCs, constant mortality levels are still observed. Therefore, a novel generation line of targeted treatment strategies is being developed, including personalized therapies with kinase inhibitors. Recent molecular studies on TCs demonstrate that kinase inhibitor-based therapies might be considered as the most promising. In the past decade, new kinase inhibitors with different mechanisms of action have been reported and approved for clinical trials. This review presents an up-to-date picture of new approaches and challenges of inhibitor-based therapies in treatment of TCs, focusing on the latest findings reported over the past two years.

Analysis of the Role of FRMD5 in the Biology of Papillary Thyroid Carcinoma.

BACKGROUND: Thyroid carcinoma (TC) is the most common endocrine system malignancy, and papillary thyroid carcinoma (PTC) accounts for >80% of all TC cases. Nevertheless, PTC pathogenesis is still not fully understood. The aim of the study was to elucidate the role of the FRMD5 protein in the regulation of biological pathways associated with the development of PTC. We imply that the presence of certain genetic aberrations (e.g., BRAF V600E mutation) is associated with the activity of FRMD5. METHODS: The studies were conducted on TPC1 and BCPAP (BRAF V600E) model PTC-derived cells. Transfection with siRNA was used to deplete the expression of FRMD5. The mRNA expression and protein yield were evaluated using RT-qPCR and Western blot techniques. Proliferation, migration, invasiveness, adhesion, spheroid formation, and survival tests were performed. RNA sequencing and phospho-kinase proteome profiling were used to assess signaling pathways associated with the FRMD5 expressional status. RESULTS: The obtained data indicate that the expression of FRMD5 is significantly enhanced in BRAF V600E tumor specimens and cells. It was observed that a drop in intracellular yield of FRMD5 results in significant alternations in the migration, invasiveness, adhesion, and spheroid formation potential of PTC-derived cells. Importantly, significant divergences in the effect of FRMD5 depletion in both BRAF-wt and BRAF-mutated PTC cells were observed. It was also found that knockdown of FRMD5 significantly alters the expression of multidrug resistant genes. CONCLUSIONS: This is the first report highlighting the importance of the FRMD5 protein in the biology of PTCs. The results suggest that the FRMD5 protein can play an important role in controlling the metastatic potential and multidrug resistance of thyroid tumor cells.

The value of the free androgen index depends on the phenotype of polycystic ovary syndrome - a single-centre experience.

INTRODUCTION: The free androgen index (FAI) values differ among patients with polycystic ovarian syndrome; however, the differences are not fully understood or known. The aim of the study was to evaluate FAI in women with polycystic ovary syndrome (PCOS) in regard to the phenotype of the PCOS and insulin resistance status. MATERIAL AND METHODS: Anthropometric, hormonal, and biochemical parameters were assessed in 312 recruited women with PCOS. The FAI values were calculated in the reproductive and metabolic phenotypes of PCOS in groups of insulin resistance status based on the homeostasis model assessment-insulin resistance (HOMA-IR) > 2.0 or fasting insulin (FI) > 10 mmol/L. To test the relationship between individual variables, Spearman's correlation analysis, the Kolmogorov-Smirnov test, and Student's t-test were used. RESULTS: The correlation between FAI values and HOMA-IR and FI was 0.42 and 0.47, respectively, in PCOS patients. A two fold higher FAI value was observed in metabolic PCOS phenotype when compared to the reproductive one (8.51 ± 5.56 vs. 4.40 ± 2.45 for HOMA-IR and 8.73 ± 6.09 vs. 4.31 ± 3.39 for FI, respectively; p < 0.05). CONCLUSIONS: PCOS patients are not a homogenous group in terms of FAI value. Patients with metabolic PCOS phenotype are characterised by two-fold higher FAI values compared with reproductive PCOS phenotype. Further studies on the metabolic and androgenic status of different types of PCOS phenotypes should be carried out.