الفهرس 
Introduction &Aim of the workOnly 14 pages are availabe for public view
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Abstract
Summary
Medullary thyroid cancer (MTC) is a form of thyroid carcinoma
which originates from the parafollicular cells (C cells), which produce
the hormone calcitonin.
Medullary tumors are the third most common of all thyroid
cancers. They make up about 3% of all thyroid cancer
cases.Approximately 25% of medullary thyroid cancer is genetic in
nature, caused by a mutation in the RET proto-oncogene. This form is
classified as familial MTC. When MTC occurs by itself it is termed
sporadic MTC. When it coexists with tumors of the parathyroid gland,
medullary component of the adrenal glands (pheochromocytoma) it is
called multiple endocrine neoplasia type 2 (MEN2).
The cause of medullary carcinoma of the thyroid (MTC) is
unknown. Unlike other types of thyroid cancer, MTC 1is less likely to be
caused by radiation therapy to the neck given to treat other cancers
during childhood.
Medullary thyroid carcinoma (MTC), a calcitonin-producing tumor
that occurs in familial and sporadic forms, can be monitored
satisfactorily with measurements of calcitonin and CEA in serum.
However, locating the tumor site may be difficult.
The primary treatment of clinically apparent hereditary or sporadic
MTC is total thyroidectomy with dissection of ipsilateral and central
neck compartments with the aim of removing all neoplastic tissue.
Chemotherapy and radiation do not work very well for this type of
cancer. Radiation is used in some patients after surgery.
Conventional chemotherapy has shown limited efficacy in patients
with MTC. Complete responses are very rare and partial responses have
been seen in less than one third of patients. The side-effect profile of
chemotherapy is often substantial, making this an unappealing option for
many patients. Single-agent regimens using doxorubicin, dacarbazine,
capecitabine, and 5-fluorouracil have been reported, with partial
response rates up to 24%–29% .Newer chemotherapeutic agents, such as
irinotecan (a topoisomerase I inhibitor) and 17-AAG (a heat shock
protein 90 inhibitor), are currently being evaluated in phase II clinical
trials
With the discovery of the ret proto-oncogene and its integral role in
the pathogenesis of MTC, a new class of therapies has been developed,
aimed at the molecular pathways central to the development and
progression of MTC.
Many of the tyrosine kinase inhibitors that are now being
investigated inhibit multiple receptors, including RET, the epidermal
growth factor receptor, and vascular endothelial growth factor (VEGF).
In April 2011, vandetanib became the first drug to be approved by
FDA for treatment of late-stage (metastatic) medullary thyroid cancer in
adult patients who are ineligible for surgery. It acts as a kinase inhibitor
of a number of cell receptors, mainly the vascular endothelial growth
factor receptor (VEGFR), the epidermal growth factor receptor (EGFR),
and the RET-tyrosine kinase.
-Cabozantinib is a small moleculeinhibitor of the tyrosine
kinasesc-Met and VEGFR2, and has been shown to reduce tumor
growth, metastasis, and angiogenesis.Cabozantinib was approved by the
U.S. FDA in November 2012 for the treatment of medullary thyroid
cancer.
Approximately 86% of those with medullary carcinoma of the
thyroid live at least 5 years after diagnosis. The 10-year survival rate is
65%