RESUMEN
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.
Asunto(s)
Carcinogénesis , Inmunoterapia/métodos , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/inmunología , Antígeno B7-H1/metabolismo , Diferenciación Celular , Transformación Celular Neoplásica , Aberraciones Cromosómicas , Reparación de la Incompatibilidad de ADN , Progresión de la Enfermedad , Factor 1 Eucariótico de Iniciación/metabolismo , Dosificación de Gen , Genómica , Humanos , Sistema de Señalización de MAP Quinasas , Mutación , Fosfatidilinositol 3-Quinasas/metabolismo , Isoformas de Proteínas , Proteínas Proto-Oncogénicas B-raf/genética , Transducción de Señal , Carcinoma Anaplásico de Tiroides/patología , Neoplasias de la Tiroides/metabolismo , Proteínas Wnt/metabolismo , Proteínas ras/metabolismoRESUMEN
In 1989, Stephen Paget proposed the 'seed and soil' theory of cancer metastasis. This theory has led to previous researchers focusing on the role of a tumour as a cancer seed and antiangiogenesis agents as cancer soil fumigant; for the latter to be effective, it is important for them to be able to distinguish cancer cells from stromal cells. However, antiangiogenesis agents have not produced dramatic survival benefits in vivo. This may be related to their inability to destroy the supporting stroma that promote cancer cell growth. Therefore, in order to effectively arrest cancer cell growth for therapeutic purposes, a paradigm shift is required in our fundamental approach to decipher the molecular events and networks in the stromal environment that cancer cells can thrive and proliferate. The pathogenesis of cancer is a multidimensional process of pathological molecular and cellular pathways, influencing different stromal properties and achieving a mutually negotiated crosstalk between cancer cells and stromal cells. This review summarises the clinical presentation of current knowledge of classical papillary thyroid carcinoma (PTC), emerging molecular diagnostics and future directions of classical PTC research.