Mechanisms of resistance to RET-directed therapies.

ABSTRACT: The association between RET and multiple endocrine neoplasia type 2 was established in 1993 and remains one of the very few oncogenes for which distinct phenotypes (medullary thyroid cancer or pheochromocytoma) are associated with the same hot-spot variants occurring in either germline or somatic DNA. Somatic RET fusion events have also been described in several cancers, including papillary thyroid cancer, non-small-cell lung cancer, breast cancer, salivary gland cancer and pancreatic cancer. Highly selective RET inhibitors have improved outcomes in RET-altered cancers and have been well-tolerated. Nevertheless, primary and acquired drug resistance has been observed, arising from distinct genomic alterations either in RET (on-target resistance) or via alternate oncogenic pathways (bypass r

SUBMITTER: Clifton-Bligh RJ 

PROVIDER: S-EPMC11798414 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature