Surrogate Markers for Antiangiogenic Therapy and Dose-Limiting Toxicities for Bevacizumab With Radiation and Chemotherapy: Continued Experience of a Phase I Trial in Rectal Cancer Patients

Hypothyroidism related to tyrosine kinase inhibitors: an emerging toxic effect of targeted therapy

“…in addition, in vitro experiments showed that veGF reduces tsH induced iodine uptake by thyroid cells, and inhibition of veGF restores iodine uptake. 42 a direct effect of sunitinib on the sodium and iodide symporter or tsH receptor has been hypothesized by mannavola et al 32 the inhibition of iodine uptake by the thyroid, caused by changes in the sodium and iodide symporter, seems to be the more likely mechanism. in fact, the authors demonstrated that the tsH receptor is not likely to be involved because other endocrine axes operating through the camP pathway were not affected.…”

“…40,41 unlike treatment with antiangiogenic tKis, bevacizumab is not associated with altered thyroid homeostasis. 42,43 other factors, such as platelet derived growth factor α and c Kit, have roles in thyroid homeostasis, but so far no data have been published. in addition, in vitro experiments showed that veGF reduces tsH induced iodine uptake by thyroid cells, and inhibition of veGF restores iodine uptake.…”

VEGF-targeted cancer therapy strategies: current progress, hurdles and future prospects

“…Bevacizumab reduced the tumor vascular density by ~50% at day 12 after the first infusion, significantly reduced the tumor blood flow [evaluated from computer tomography (CT) scans] and the number of viable circulating endothelial cells (CECs) and progenitor cells (CPCs). The tumors in both the low-dose [45] and the high-dose bevacizumab [46] infusion groups had a less hyperemic or hemorrhagic appearance. However, there was no significant tumor regression after bevacizumab treatment, as determined by flexible sigmoidoscopy examination, which enables macroscopic visualization of the rectal cancer.…”

“…The reduction in tumor vasculature led to a significant increase in cancer cell apoptosis. Interestingly, it also led to the emergence of a more mature (pericyte-covered) vasculature [45,46] and increased cancer cell proliferation [46] (Figure 2). Twelve days after bevacizumab therapy alone, the tumor interstitial fluid pressure (IFP) was consistently decreased, particularly in patients with high baseline values [45,46].…”

“…Interestingly, it also led to the emergence of a more mature (pericyte-covered) vasculature [45,46] and increased cancer cell proliferation [46] (Figure 2). Twelve days after bevacizumab therapy alone, the tumor interstitial fluid pressure (IFP) was consistently decreased, particularly in patients with high baseline values [45,46]. This suggests that in human tumors, similar to mouse models [47,48], the tumor microenvironment is normalized by the reduction of the excess abnormal vasculature and is potentially sensitized to subsequent cytotoxic therapy.…”