Molecular features of aggressive thyroid cancer

Abstract

Poorly differentiated thyroid cancer (PDTC) and anaplastic thyroid cancer (ATC) have a worse prognosis with respect to well differentiated TC, and the loss of the capability of up-taking 131I is one of the main features characterizing aggressive TC. The knowledge of the genomic landscape of TC can help clinicians to discover the responsible alterations underlying more advance diseases and to address more tailored therapy. In fact, to date, the antiangiogenic multi-targeted kinase inhibitor (aaMKIs) sorafenib, lenvatinib, and cabozantinib, have been approved for the therapy of aggressive radioiodine (RAI)-resistant papillary TC (PTC) or follicular TC (FTC). Several other compounds, including immunotherapies, have been introduced and, in part, approved for the treatment of TC harboring specific mutations. For example, selpercatinib and pralsetinib inhibit mutant RET in medullary thyroid cancer but they can also block the RET fusion proteins-mediated signaling found in PTC. Entrectinib and larotrectinib, can be used in patients with progressive RAI-resistant TC harboring TRK fusion proteins. In addition FDA authorized the association of dabrafenib (BRAFV600E inhibitor) and trametinib (MEK inhibitor) for the treatment of BRAFV600E-mutated ATC. These drugs not only can limit the cancer spread, but in some circumstance they are able to induce the re-differentiation of aggressive tumors, which can be again submitted to new attempts of RAI therapy. In this review we explore the current knowledge on the genetic landscape of TC and its implication on the development of new precise therapeutic strategies.

Targeting nerve growth factor-mediated osteosarcoma metastasis: mechanistic insights and therapeutic opportunities using larotrectinib

“…First-generation tropomyosin receptor kinase (TRK) inhibitors, larotrectinib and entrectinib, are ATP-competitive inhibitors that bind specifically effective in the treatment of various cancers, including infantile fibrosarcoma [48], anaplastic thyroid cancer [49]. Robert et al demonstrated that inhibiting compensatory In summary, this study confirmed that NGF suppresses the synthesis of miR-92a-1-5p via the MEK/ERK signaling cascade, thereby promoting the MMP-2-dependent migration of osteosarcoma cells.…”

Correlation analysis between BRAFV600E mutation and ultrasonic and clinical features of papillary thyroid cancer

“…Most mutations occur in the 1799th nucleotide of exon 15, resulting in the replacement of valine with glutamic acid in the 600th codon of protein translation, which causes abnormal phosphorylation, activates the MAPK signaling pathway, regulates cell proliferation and differentiation, and promotes tumorigenesis and development [ 23 , 24 ]. Some studies have suggested that BRAF V600E mutations are associated with aggressive behavior and adverse prognosis, such as multiple carcinomas, lymphatic metastasis, membrane invasion, high TNM stage, and prognosis [ [25] , [26] , [27] , [28] ]. However, some studies suggest that BRAF V600E mutations are not significantly associated with prognosis [ 29 , 30 ].…”

Lenvatinib-Loaded Poly(lactic-co-glycolic acid) Nanoparticles with Epidermal Growth Factor Receptor Antibody Conjugation as a Preclinical Approach to Therapeutically Improve Thyroid Cancer with Aggressive Behavior

“…This loss of iodine uptake represents a significant survival rate reduction in patients (60 to 70%) five years after diagnosis [1][2][3]. In these tumors subtypes, including ATC, poorly differentiated thyroid carcinoma (PDTC), and RAI-refractory WDTC patients, the identification of the oncogenic driver mutations, able to activate specific kinases, has allowed the use of tyrosine kinase inhibitors (TKIs) as a therapeutic strategy [4][5][6][7]. For instance, the TKI lenvatinib demonstrated a significantly longer median progression-free survival (PFS) compared with both sorafenib and the placebo group; PFS time for lenvatinib was 18.3 months, whereas it was only 3.6 months for the placebo group (p < 0.001).…”