Article ID Journal Published Year Pages File Type
2101104 Biochimica et Biophysica Acta (BBA) - Reviews on Cancer 2009 10 Pages PDF
Abstract

B-RafV600E, an oncogenic protein kinase, is the most frequent genetic alteration in papillary thyroid carcinomas (PTC). PTC represents 80–90% of all thyroid cancers and over the past five years, more than 200 manuscripts have been published about the relationship between “B-RafV600E and thyroid cancer”. B-RafV600E genetically arises from a transversion point mutation (valine-to-glutamate substitution at amino acid residue-600, V600E) and leads to over activation of the mitogen-activated protein kinases (MAPK) signaling pathway. The MAPK pathway is essential for transmitting proliferation signals generated by cell surface receptors and cytoplasmic signaling elements to the nucleus. In many cancers, including thyroid cancer, B-RafV600E appears to play a crucial role in cell proliferation, survival and de-differentiation. In thyroid cancer, the V600E mutation occurs with greater frequently in aggressive subtypes of PTC, and in individuals that present at advanced stages of disease with extra-thyroidal extension and/or lymph node metastases. B-RafV600E is considered a marker of aggressive disease in both PTC (> 1 cm) and micro-PTC (≤ 1 cm), and interestingly, is associated with both loss of I-131 avidity and PTC recurrence. Though treatment of patients with thyroid cancer is usually successful and most patients are rendered disease-free, to date there are no effective therapies for patients with invasive, non-radioiodine sensitive tumors or metastatic disease. In this article we will review the relation between B-RafV600E and PTC, as well as both non-selective and selective pharmacological agents currently under investigation for treatment of B-RafV600E positive PTC.

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