4 research outputs found
Molecular mechanisms of medullary thyroid carcinoma, current approaches in diagnosis and treatment
Medullary thyroid carcinoma is the most
common cause of death among patients with multiple
endocrine neoplasia (MEN) 2. Dominant-activating
mutations in the RET proto-oncogene have been shown
to have a central role in the development of MEN 2 and
sporadic medullary thyroid cancer (MTC): about half of
sporadic MTCs are caused by somatic genetic changes
of the RET oncogene. Inactivating mutations of the same
gene lead to Hirschprung disease and other
developmental defects. Thus, RET genetic changes lead
to phenotypes that largely depend on their location in the
gene and the function and timing of developmental
expression of the RET protein. The reproducibility of the
phenotype caused by each RET genotype led to MEN
2/MTC being among the first conditions in Medicine
where a drastic measure is applied to prevent cancer,
following genetic testing: thyroidectomy is currently
routinely done in young children that are carriers of
MTC-predisposing RET mutations. RET inhibitors have
been also developed recently and are used in various
types of thyroid and other cancers. This report reviews
the RET involvement in the etiology of MEN 2 and MTC and updates the therapeutic approach in preclinical
and clinical studies