Abstract
Thyroid cancer is the most prevalent endocrine malignancy that comprises mostly indolent differentiated cancers (DTCs) and less frequently aggressive poorly differentiated (PDTC) or anaplastic cancers (ATCs) with high mortality. Utilisation of next-generation sequencing (NGS) and advanced sequencing data analysis can aid in understanding the multi-step progression model in the development of thyroid cancers and their metastatic potential at a molecular level, promoting a targeted approach to further research and development of targeted treatment options including immunotherapy, especially for the aggressive variants. Tumour initiation and progression in thyroid cancer occurs through constitutional activation of the mitogen-activated protein kinase (MAPK) pathway through mutations in BRAF, RAS, mutations in the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) pathway and/or receptor tyrosine kinase fusions/translocations, and other genetic aberrations acquired in a stepwise manner. This review provides a summary of the recent genetic aberrations implicated in the development and progression of thyroid cancer and implications for immunotherapy.
Highlights
Thyroid cancer (TC) is the most common endocrine malignancy, constituting 2.1% of all newly diagnosed cancer cases worldwide [1]
Benign and intermediate (NIFTP) entities develop from follicular epithelial cells, and it is theorised that differentiated cancers (DTCs) develop from benign and intermediate lesions (NIFTP)
90% of mutations are mutually exclusive activating mutations in oncogenes Rat sarcoma (RAS) (~13%) and BRAF (~60%), and rearrangements involving Rearranged during transfection (RET), Anaplastic lymphoma kinase (ALK) and NTRK genes (~5%); whilst the remaining 10% are loss-of-function mutations affecting tumour suppressor genes such as Phosphatase and tensin homolog (PTEN), PPARγ and Tumour protein 53 (TP53) [17,18,19] Targeted therapies are in use for tumours with some of these mutations
Summary
Thyroid cancer (TC) is the most common endocrine malignancy, constituting 2.1% of all newly diagnosed cancer cases worldwide [1]. Between 1982 and 2019, the age-standardised incidence rate of thyroid cancer increased by 392% (from 2.7 to 13 per 100,000 persons) [4]. This increase is in both genders, all age groups and ethnicities with papillary thyroid carcinomas accounting for the most cases [5,6]. The increased incidence is attributed to overdetection of small indolent tumours and a concurrent increase in subsequent surgical intervention rates; patients are overtreated for low-risk tumours [5,7]. It is imperative to identify ‘high-risk’ patients to guide appropriate treatment and prevent overtreatment of ‘low-risk’ patients
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
