Medullary thyroid cancer is an indolent neuroendocrine tumor that frequently presents with disseminated disease. While locally advanced tumor in the neck and mediastinum can be treated with surgery either for palliative or curative intent, distant metastases are not often amenable to operative excision. Metastatic MTC has a similarly poor response to radiotherapy and chemotherapy. Viable therapeutic options for distant metastatic disease are still absent. Survival rate after discovery of distant metastasis has been around 25% at 5 years and 10% after 10 years, though this has more recently been improved due to earlier discovery of the malignancy (12, 13). However, new molecular targets have expedited the oncologic research towards its goal to develop therapeutic agents effective in disseminated disearse (14 ).
Discovery of new therapeutic targets is now possible for MTC. Thus far, these potential targets include kinase inhibitors (RET/PTC) or signaling kinases such as vascular endothelial growth factor receptor (VEGFR), with a growing number of studies involving the molecular pathways involved in thyroid cancer malignancy (15 ). Ras, a G protein, is an initiator of the Ras/Raf/mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway. Phosphorylation of GDP activates Ras that in turn activates Raf. Raf comprises of three cytosolic kinases of which Raf-1 is more imperative among three for aspects of cell differentiation (1).
Once Raf activation is initiated, it further initiates MEK and ERK, which are salient in cell differentiation, growth and endurance (5, 16). We have shown recently that expression of estradiol-inducible active raf1 in pancreatic carcinoid BON cells and MTC cells leads to growth inhibition and reduction in NE hormone production (4). However, the role of MEK signaling...