Overwhelming rapid metabolic and structural response to apatinib in radioiodine refractory differentiated thyroid cancer

Yang, Lin; Wang, Chen; Gao, Wen; Cui, Ruixue; Liang, Jun

doi:10.18632/oncotarget.15036

Cited by 54 publications

(44 citation statements)

References 37 publications

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“…Apatinib is a novel TKI highly selective for VEGFR2 with good antitumor effects in various types of solid tumors. Apatinib was shown to be safe and highly efficacious in a small number of patients with radioiodine-refractory differentiated thyroid cancer (13). In this report, we investigated the potential therapeutic effect of apatinib on PTC and the mechanism of apatinib in vitro and in vivo.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, apatinib has shown antitumor effects in various types of solid tumors in a number of ongoing phase II and III clinical trials (11,12). Lin et al (13) reported that apatinib showed promising efficacy in a small number of patients with radioiodine-refractory differentiated thyroid cancer. However, the antitumor mechanism of apatinib in PTC is unclear.…”

Section: Introductionmentioning

confidence: 99%

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Apatinib Inhibits Cell Proliferation and Induces Autophagy in Human Papillary Thyroid Carcinoma via the PI3K/Akt/mTOR Signaling Pathway

et al. 2020

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Background: Patients with metastatic radioiodine-refractory papillary thyroid carcinoma (PTC) have limited treatment options and a poor prognosis. There is an urgent need to develop new drugs targeting PTC for clinical application. Apatinib, a novel small-molecule tyrosine kinase inhibitor (TKI), is highly selective for vascular endothelial growth factor receptor-2 (VEGFR2) and exhibits antitumor effects in a variety of solid tumors. Although apatinib has been shown to be safe and efficacious in radioiodine-refractory differentiated thyroid cancer, the mechanism underlying its antitumor effect is unclear. In this report, we explored the effects of apatinib on PTC in vitro and in vivo.Methods: VEGFR2 expression levels were evaluated by immunohistochemistry (IHC), qPCR, and western blotting (WB). The effects of apatinib on cell viability, colony formation, and migration in the Transwell assay were assessed in vitro, and its effect on tumor growth rate was assessed in vivo. In addition, the levels of proteins in signaling pathways were determined by WB. Finally, the autophagy level was assessed by WB, immunofluorescence (IF), and transmission electron microscopy.Results: We found that high VEGFR2 expression is associated with tumor size, T stage, and lymph node metastasis in patients with PTC and that apatinib inhibits PTC cell growth, promotes apoptosis, and induces cell cycle arrest through the PI3K/Akt/mTOR signaling pathway. Moreover, apatinib induces autophagy, and pharmacological inhibition of autophagy or small interfering RNA (siRNA)-mediated targeting of autophagy-associated gene 5 (ATG5) can further increase PTC cell apoptosis.Meng et al. Effects of Apatinib in PTCConclusion: Our data suggest that apatinib can induce apoptosis and autophagy via the PI3K/Akt/mTOR signaling pathway for the treatment of PTC and that autophagy is a potential novel target for future therapy in resistant PTC.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Apatinib Inhibits Cell Proliferation and Induces Autophagy in Human Papillary Thyroid Carcinoma via the PI3K/Akt/mTOR Signaling Pathway

et al. 2020

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“…Apatinib, a highly selective tyrosine kinase inhibitor of VEGFR-2, was proven to have an anti-tumor effect in various tumors 5 – 7 , 33 . Recently, apatinib has demonstrated a promising therapeutic effect for radioiodine refractory differentiated thyroid cancer 34 , which suggests a novel method for ATC treatment. We previously confirmed that apatinib could significantly reduce ATC angiogenesis in a dose- and time-dependent manner.…”

Section: Discussionmentioning

confidence: 99%

Apatinib-induced protective autophagy and apoptosis through the AKT–mTOR pathway in anaplastic thyroid cancer

et al. 2018

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Apatinib, an inhibitor of vascular endothelial growth factor receptor-2, has been shown to promote anti-cancer action across a wide range of malignancies, including gastric, lung, and breast cancers. Our previous study showed that apatinib increases apoptosis in anaplastic thyroid carcinoma (ATC), but the direct functional mechanism of tumor lethality mediated by apatinib is still unknown. In this study, we demonstrated that apatinib induced both autophagy and apoptosis in human ATC cells through downregulation of p-AKT and p-mTOR signals via the AKT/mTOR pathway. Moreover, inhibition of apatinib-induced autophagy increased apatinib-induced apoptosis in ATC cells, and additional tumor suppression was critically produced by the combination of apatinib and the autophagy inhibitor chloroquine in vivo and in vitro. These findings showed that both autophagy and AKT/mTOR signals were engaged in ATC cell death evoked by apatinib. ATC patients might benefit from the new anti-cancer drug, and molecular targeted treatment in combination with autophagy inhibitors shows promise as a treatment improvement.

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“…The patient in our study has thus far achieved disease-free status for 12 months. Apatinib has produced promising clinical outcomes in several other types of cancer [ 39 – 43 ], and has a high binding affinity relative to other anti-angiogenic drugs. For example, apatinib ligand-receptor binding is 10 times greater than that of sorafenib [ 44 , 45 ].…”

Section: Discussionmentioning

confidence: 99%

Advanced alveolar soft part sarcoma responds to apatinib

et al. 2017

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Alveolar soft part sarcoma (ASPS) is a rare, hypervascular soft tissue sarcoma with a low chemotherapy response rate. Here, we report an ASPS case with multiple lung metastases on initial presentation. The primary tumor, a hypervascular soft tissue mass 4.1×3.2×2.0 cm, located in the right thigh, was resected prior to chemotherapy. The patient suffered disease progression after two cycles of gemcitabine-docetaxel treatment. Immunohistochemical examination of the tumor tissue revealed strong positive staining for vascular endothelial growth factor (VEGF) and VEGF receptor-2 (VEGFR-2). The patient was subsequently treated with apatinib (500 mg/day), a specific VEGFR-2 inhibitor. Treatment was well tolerated, and the patient exhibited a partial response, with the lung metastases reduced in size and number after one month of therapy. To date, 12-month progression-free survival has been achieved. Apatinib may provide an additional treatment option for metastatic ASPS, particularly in cases resistant to other chemotherapeutic options. Furtherstudies with more cases with longer follow-up times will be necessary to determine the clinical efficacy of apatinib for treatment of ASPS.

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Overwhelming rapid metabolic and structural response to apatinib in radioiodine refractory differentiated thyroid cancer

Cited by 54 publications

References 37 publications

Apatinib Inhibits Cell Proliferation and Induces Autophagy in Human Papillary Thyroid Carcinoma via the PI3K/Akt/mTOR Signaling Pathway

Apatinib Inhibits Cell Proliferation and Induces Autophagy in Human Papillary Thyroid Carcinoma via the PI3K/Akt/mTOR Signaling Pathway

Apatinib-induced protective autophagy and apoptosis through the AKT–mTOR pathway in anaplastic thyroid cancer

Advanced alveolar soft part sarcoma responds to apatinib

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