Preliminary data of VEGF-A and VEGFR-2 polymorphisms as predictive factors of radiological response and clinical outcome in iodine-refractory differentiated thyroid cancer treated with sorafenib

Antitumor Effect of 131I-Labeled Anti-VEGFR2 Targeted Mesoporous Silica Nanoparticles in Anaplastic Thyroid Cancer

“…VEGF’s well-established role in angiogenesis means that radiolabeled ligands, such as bevacizumab, which targets the VEGF receptor (VEGFR), have been developed successfully for early and sensitive lesion detection using positron emission tomography (PET) and single-photon emission computed tomography (SPECT) imaging techniques. VEGFR-2 exerts most of the functions of VEGF in blood vessel endothelial cells, and is responsible for proliferation through the activation of the mitogen-activated protein kinase pathway, migration of endothelial vessels, and the promotion of angiogenesis and vascular growth [7, 8]. VEGF expression is upregulated in ATC cells from epithelial origin compared with that in normal thyroid tissue [9–11].…”

Toward predictive biomarkers of response to kinase inhibitor therapies in differentiated thyroid cancer

“…Moreover, these systemically administered therapeutics are expected to inhibit targets not only in tumor, but also in host tissues, with potential therefore for their efficacies to be affected not only by tumor-specific, but also by host-specific, alterations [1]. Accordingly, in their small preliminary study, Marotta et al [4] posed the question of whether specific germline single-nucleotide polymorphisms (SNPs) of the VEGF-A and VEGFR-2 genes (dominant angiogenic regulators potentially capable of altering sensitivities to VEGFRtargeted kinase inhibitors) might correlate with response to sorafenib treatment in patients with RAIR DTC. Six SNPs were selected for analysis based on previous reported studies in cancers other than thyroid (other solid tumors and lymphoma).…”

“…The study by Marotta et al [4] importantly targeted identification of possible predictive biomarkers of response to sorafenib therapy in RAIR DTC, an area yet to be fully explored. To date, searches for predictive biomarker of kinase inhibitor response in RAIR DTC have, however, almost exclusively examined somatic (tumor) mutations/ alterations [5], with attempts to elucidate germline SNP predictors of response largely ignored.…”

“…To date, searches for predictive biomarker of kinase inhibitor response in RAIR DTC have, however, almost exclusively examined somatic (tumor) mutations/ alterations [5], with attempts to elucidate germline SNP predictors of response largely ignored. The investigation of the possibility that heterogeneity of germline VEGF/ VEGFR SNPs might predict response to sorafenib therapy is thus an especially provocative aspect of the study of Marotta et al [4], as any identified positive association-if robust-might be used to individualize therapy even in the absence of interrogation of tumor tissue and without the need for biopsy. Such an approach has potential to aid in better selection of patients for sorafenib treatment, sparing patients with lesser probability of response undesirable side effects, potentially seeding them instead to clinical trials or therapy based on their somatic tumor mutations (e.g., BRAFV600E).…”

“…In addition to the approach taken by Marotta et al [4], other germline biomarkers might alternatively be sought in the form of explorations of whether pharmacogenomics heterogeneity of SNPs of relevance to metabolism might also contribute to differential response to kinase inhibitor therapy in RAIR DTC. Continued research into the elucidation of candidate predictive germline markers of therapeutic response is much needed.…”