Advances in the Prognosis and Treatment of Medullary or Anaplastic Thyroid Cancer

Advances in the Prognosis and Treatment of Medullary or Anaplastic Thyroid Cancer

Jordan Karin , Schmoll Hans-Joachim , Voigt Wieland
US ONCOLOGY - VOLUME 5 ISSUE 1
Published: July 2009
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Abstract
Despite being the most common endocrine malignancy, thyroid cancer accounts for approximately only 1% of all reported malignancies. Anaplastic thyroid cancer (ATC) is one of the most aggressive forms and accounts for 2–5% of cases of all thyroid cancers, while medullary thryroid cancer (MTC) accounts for 3–5%. As a result of their distinct clinical and molecular characteristics, it is necessary to pursue different multimodal strategies. Significant progress in decoding the molecular biology of thyroid cancer has been made; however, the outcomes of ATC are still dismal. Although aggressive multimodal locoregional treatment reduces the rate of relapse, patients continue to die of metastatic disease owing to the lack of active systematic treatment regimes. Therapy for MTC took an optimistic turn with the discovery of the RET protooncogene, which led to the introduction of targeted agents in the treatment concept. Although these emerging therapies have raised hopes, their impact on clinical outcome needs to be clarified by future randomised trials.

Thyroid cancer accounts for approximately only 1% of all reported malignancies, but is the most common endocrine malignancy.1 It is of either follicular cell origin with well-differentiated papillary thyroid cancer and follicular thyroid cancer, poorly differentiated thyroid cancer (PDTC), and anaplastic thyroid cancer (ATC), or of parafollicular C-cell origin with medullary thyroid cancer (MTC).2 ATC, one of the most aggressive malignancies in humans, accounts for approximately 2–5% and MTC for approximately 3–5% of all thyroid cancers.2 Owing to their distinct clinical and molecular characteristics, different multimodal treatment strategies have to be pursued.

While ATC is characterized by an almost fatal outcome, with survival that rarely exceeds one year regardless of the available therapy,1 unselected patients suffering from MTC have an overall 10-year survival of approximately 70% following primary surgery.3,4 However, little effective therapy has existed until recently for patients with unresectable MTC.4 Because of the rarity of the disease, large-scale prospective studies are scarce and thus, until now, most progress has come from retrospective analysis of treatment data collected over several decades. While surgery is the only curative treatment option in MTC,4 the exact role and sequence of surgery, radiation, and chemotherapy in the multimodal treatment strategy in ATC is still a matter of debate.

Recent pre-clinical studies have identified a large battery of molecular alterations in thyroid cancer that provide the basis for the development of molecular targeted therapy for patients with progressive disease.2,4–6 Several novel compounds with promising activity in pre-clinical studies are currently being evaluated in small clinical trials, with promising results overall. However, the impact of these emerging therapies on the clinical course of the disease is yet to be defined. This short article will summarize the data on multimodal treatment strategies in ATC and provide an overview of the new treatment options for MTC and ATC, with an emphasis on molecular targeted treatment.

Molecular Targets in Thyroid Cancer
Increased knowledge of the molecular biology of thyroid cancer has led to the development of new potential treatment options for patients suffering from progressive disease. Several alterations in cell-cycle control, growth factor signal transduction, or regulation of apoptosis crucial for the development of ATC or MTC have been identified in cell line studies and analysis of clinical specimens (see Figure 1).2,5

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Keywords:
Anaplastic thyroid cancer, medullary thyroid cancer, targeted drugs, multimodality treatment

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