Molecular genetics of medullary thyroid carcinoma: the quest for novel therapeutic targets.

Medullary thyroid carcinoma (MTC) is a rare tumour arising from neural crest-derived parafollicular C cells. Metastatic MTC patients are incurable because the cancer does not respond to radiotherapy or chemotherapy. The RET proto-oncogene plays a key role in the development of MTC. However, one half of sporadic MTC do not carry RET mutations. Mice models and early evidence obtained in human samples suggest that other genes, including those encoding components of the RB (retinoblastoma) and TP53 tumour suppressor pathways, may be involved in MTC formation. Here we review the data on the involvement of genes acting in the RET and RB/TP53 pathways in MTC. Understanding genetic lesions that occur in MTC is a prerequisite to identifying molecular therapeutic targets in MTC and to improving the efficacy of RET-targeted therapies.