RET kinase inhibitors for the treatment of RET-altered thyroid cancers: Current knowledge and future directions.
Ann Endocrinol (Paris)
; 85(2): 118-126, 2024 Apr.
Article
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| MEDLINE
| ID: mdl-38342224
ABSTRACT
RET gain-of-function mutations are the most common drivers in medullary thyroid carcinoma, while RET fusions are identified in 5-10% of papillary thyroid carcinomas. Thus, RET plays a major role in the tumorigenesis of thyroid neoplasia, making it a valuable therapeutic target. Over a decade ago, multikinase inhibitors (MKIs) were first shown to have variable degrees of anti-RET activity. Despite some clinical efficacy in RET-altered thyroid cancers, significant off-target activity of MKIs led to marked toxicities limiting their use. More recently, two potent, highly selective RET inhibitors, selpercatinib and pralsetinib, were shown to have notable efficacy in RET-altered cancers, associated with more tolerable side effect profiles than those of MKIs. However, these treatments are non-curative, and emerging evidence suggests that patients who progress on therapy acquire mutations conferring drug resistance. Thus, the quest for a more definitive treatment for advanced, RET-altered thyroid cancers continues. This year we celebrate the 30th anniversary of the association of germline mutations of the RET proto-oncogene with the multiple endocrine neoplasia (MEN) type 2 syndromes. In this timely review, we summarize the current state-of-the-art treatment strategies for RET-altered thyroid cancers, their limitations, as well as future therapeutic avenues.
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Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Neoplasias de la Tiroides
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Carcinoma Neuroendocrino
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Neoplasia Endocrina Múltiple Tipo 2a
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Ann Endocrinol (Paris)
/
Ann. endocrinol
/
Annales d' endocrinologie
Año:
2024
Tipo del documento:
Article