Review: Thyroid cancer: emerging role for targeted therapies

Abstract

The histology and clinical behavior of thyroid cancer are highly diverse. Although most are indolent tumors with a very favorable outcome with the current standard of care therapy, a small subset of tumors may be among the most lethal malignancies known to man. While surgery and radioactive iodine are the standard of care for differentiated thyroid cancers (DTC) and are effective in curing a majority of such patients, those with iodineresistant cancers pose a great challenge for clinicians, as these patients have limited treatment options and poor prognoses. Medullary thyroid carcinoma (MTC) has no effective systemic therapy despite the genetic and signaling defects that have been well characterized for the last two decades. Anaplastic thyroid cancer (ATC) is one of the most aggressive solid tumors that remains fatal despite conventional multimodality therapy. Increased understanding of the pathogenesis of papillary thyroid carcinoma, the most common type of DTC, as well as ATC, has led to the development of targeted therapies aimed at signaling pathways and angiogenesis that are critical to the development and/or progression of such tumors. Development of tyrosine kinase inhibitors targeting known pathogenetic defects in MTC has led to testing of such agents in the clinic. Numerous clinical trials have been conducted over the last 5 years to examine the effects of these targeted molecular therapies on the outcomes of patients with iodine-refractory DTC, MTC and ATC. Conduction of such trials in the last few years represents a major breakthrough in the field of thyroid cancer. Several trials testing targeted therapies offer promise for setting new standards for the future of patients with progressive thyroid cancer. The purpose of this paper is to outline the recent advances in understanding of the pathogenesis of thyroid cancer and to summarize the results of the clinical trials with these targeted therapies.

Thyroid cancer: SEOM clinical guidelines

“…In addition to these mutations, MTCs are associated with other conditions of the tumor microenvironment, such as high vascularization, as well as high levels of vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and the platelet-derived growth factor (PDGF). This fact shows that these tumors show a high capillary microdensity allowing neoplastic cells to enter the blood vessels and spread to distant metastases [ 15 ].…”

Resistance to Src inhibition alters the BRAF-mutant tumor secretome to promote an invasive phenotype and therapeutic escape through a FAK>p130Cas>c-Jun signaling axis

“…Significant morbidity and mortality remains a problem for advanced thyroid cancer patients with distant metastatic disease, and anaplastic thyroid cancer (ATC), which remains one of the most lethal human cancers (1,2). There has been much interest in targeting the MAP kinase pathway in thyroid cancer due to a high prevalence of BRAF and RAS mutations (3,4), and while BRAF-directed therapies are promising (5–8), there is a need for unique therapeutic approaches that will be effective in both BRAF wild-type and mutant cancers (2,3).…”

Molecular profiling of thyroid cancer subtypes using large-scale text mining

“…These "targeted therapeutics" of thyroid cancer are being rapidly developed [ 6 , 7 ]. Several potential drugs are currently in preclinical testing or in clinical use [ 8 , 9 ].…”