Abstract
BackgroundAnaplastic thyroid cancer (ATC) is a rare, lethal disease associated with a median survival of 6 months despite the best multidisciplinary care. Surgical resection is not curative in ATC patients, being often a palliative procedure. Multidisciplinary care may include surgery, loco-regional radiotherapy, and systemic therapy. Besides conventional chemotherapy, multi kinase-targeted inhibitors are emerging as novel therapeutic tools. The numerous molecular alteration detected in ATC are targets for these inhibitors. The aim of this review is to determine the prevalence of the major genetic alterations occurring in ATC and place the results in the context of the emerging kinase-targeted therapies.MethodsThe study is based on published PubMed studies addressing the prevalence of BRAF, RAS, PTEN, PI3KCA and TP53 mutations and RET rearrangements in ATC.Results21 articles dealing with 652 genetic analyses of the selected genes were used. The overall prevalence determined were the following: RET/PTC, 4%; BRAF, 23%; RAS, 60%; PTEN, 16%; PI3KCA, 24%; TP53, 48%. Genetic alterations are sometimes overlapping.ConclusionsMutations of BRAF, PTEN and PI3KCA genes are common in ATC, with RAS and TP53 being the most frequent. Given ATC genetic complexity, effective therapies may benefit from individualized therapeutic regimens in a multidisciplinary approach.
Highlights
Thyroid cancer is the most prevalent endocrine malignancy accounting for 1% of cancers worldwide
Thyroid cancer is characterized by several genetic alterations along these two pathways, including rearrangements of the RET tyrosine receptor kinase, activating point mutations in the BRAF serine/ threonine kinase, in the RAS proto-oncogenes, in the catalytic subunit of the phosphatidyl-inositol 3-Kinase (PI3KCA), or inactivating mutations in the tumor suppressors phosphatase and tensin homolog (PTEN) and TP53 (Table 1)
BRAFV600E was the only BRAF mutation considered by the 7 studies analyzed
Summary
Thyroid cancer is the most prevalent endocrine malignancy accounting for 1% of cancers worldwide. The use of effective diagnostic tools such as ultrasound (US) and fine-needle cytology (FNC) [3,4,5] has increased the detection of small and well efficacy in the case of ATC as well as of other more common solid tumors [12,13,14] Alternative strategies such as immunotherapy are under investigation, but still far from clinical practice [15]. The last decade has seen advances in the understanding of the molecular basis of thyroid cancer, leading to the application of new pharmacological treatments with inhibitors of kinases [23,24,25] These drugs are multi-target agents with inhibitory activity of receptors involved in the angiogenesis or inhibitors of kinases involved in thyroid cancer development. The aim of this review is to determine the prevalence of the major genetic alterations occurring in ATC and place the results in the context of the emerging kinase-targeted therapies
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