Multikinase inhibitor sorafenib induces skin toxicities in tumor-bearing mice

Tian, Anmin; Lu, Haizhen; Zhang, Jingxuan; Fu, Shilan; Jiang, Zaoli; Lam, Wing; Guan, Fulan; Chen, Linlin; Li, Feng; Cheng, Yung‐Chi

doi:10.1007/s00280-018-3575-y

Cited by 3 publications

(1 citation statement)

References 20 publications

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“…It has also been used to treat patients with hepatocellular carcinoma (HCC), since 2007 [6], and finally in patients with progressive, locally advanced or metastatic, differentiated (papillary/follicular/Hürthle cell) thyroid cancer, resistant to treatment with radioactive iodine, since 2013 [7]. Additionally, the efficacy of the drug has been assessed in many clinical trials conducted on adults with various types of cancer, including breast cancer, salivary gland cancer, melanoma, non-small cell lung cancer, glioma [8][9][10][11][12][13]. Nowadays the drug is mostly used to treat hepatocellular carcinoma (HCC) due to limited possibilities of treatment of the advanced stages of this cancer [14,15].…”

Section: Introductionmentioning

confidence: 99%

In vivo assessment of the drug interaction between sorafenib and paracetamol in rats

Karbownik

Sobańska

Grabowski

et al. 2020

Cancer Chemother Pharmacol

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Purpose Sorafenib is a multi-targeted tyrosine kinase inhibitor (TKI) used for the treatment of advanced renal cell carcinoma, hepatocellular carcinoma and radioactive iodine resistant thyroid carcinoma. Neoplastic diseases are the cause of pain, which may occur regardless of the stage of the disease. Paracetamol is a non-opioid analgesic used alone or in combination with opioids for the treatment of cancer pain. Numerous studies have pointed out changes in the pharmacokinetic parameters of TKIs when co-administered with paracetamol. The aim of the study was to assess drug-drug interactions (DDIs) between sorafenib and paracetamol. Methods Rats were divided into three groups, each consisting of eight animals. The first group received sorafenib (II S), the second group received sorafenib + paracetamol (I S+PA), whereas the third group received only paracetamol (III PA). A single dose of sorafenib (100 mg/kg b.w.) and paracetamol (100 mg/kg b.w.) was administered orally. The plasma concentrations of sorafenib and its metabolite-N-oxide as well as paracetamol and its glucuronide and sulphate metabolites were measured using validated high-performance liquid chromatography (HPLC) method with ultraviolet detection. Results The co-administration of sorafenib and paracetamol increased the maximum concentration (C max) of paracetamol by 33% (p = 0.0372). In the I S+ PA group the C max of paracetamol glucuronide was reduced by 48% (p = < 0.0001), whereas the C max of paracetamol sulphate was higher by 153% (p = 0.0012) than in the III PA group. Paracetamol increased sorafenib and sorafenib N-oxide C max by 60% (p = 0.0068) and 83% (p = 0.0023), respectively. Conclusions A greater knowledge of DDI between sorafenib and paracetamol may help adjust dose properly and avoid toxicity effects in individual patients.

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Section: Introductionmentioning

confidence: 99%

In vivo assessment of the drug interaction between sorafenib and paracetamol in rats

Karbownik

Sobańska

Grabowski

et al. 2020

Cancer Chemother Pharmacol

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Solute Carrier Transportome in Chemotherapy-Induced Adverse Drug Reactions

Anderson

Huang

Lustberg

et al. 2020

Reviews of Physiology, Biochemistry and Pharmacology

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Sorafenib inhibits ovarian cancer cell proliferation and mobility and induces radiosensitivity by targeting the tumor cell epithelial–mesenchymal transition

et al. 2022

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Sorafenib, a pan-protein kinase inhibitor, inhibits the activity of various kinases (like vascular endothelial growth factor, platelet-derived growth factor, and rapidly accelerated fibrosarcoma) and clinically has been used to treat different human cancers. This study investigated its antitumor activity in ovarian cancer and the underlying molecular events. To achieve that, ovarian cancer SKOV-3 cells were treated with or without sorafenib (10 µM), transforming growth factor (TGF)-β1 (10 ng/mL), sorafenib (10 µM) + TGF-β1 (10 ng/mL), and TGF-β1 (10 ng/mL) + Ly2157299 (5 µM), followed by 8-Gy radiation. The cells were then subjected to cell viability, wound healing, Transwell, caspase-3 activity, and western blot assays. TGF-β1 treatment enhanced ovarian cancer cell epithelial–mesenchymal transition (EMT), whereas sorafenib and a selective TGF-β1 inhibitor Ly2157299 reversed tumor cell EMT, invasion, and expression of EMT markers (E-cadherin and vimentin). Sorafenib and Ly2157299 treatment also significantly reduced the tumor cell viability. Furthermore, both sorafenib and Ly2157299 significantly enhanced ovarian cancer cell radiosensitivity, as assessed by a caspase-3 activity assay. In conclusion, sorafenib inhibited ovarian cancer cell proliferation and mobility and induced tumor cell radiosensitivity. Molecularly, sorafenib could inhibit the TGF-β1-mediated EMT. Future studies will assess sorafenib anti-ovarian cancer activity plus TGF-β1 inhibitors in ovarian cancer in vivo.

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Multikinase inhibitor sorafenib induces skin toxicities in tumor-bearing mice

Abstract: The severity of skin lesions was positively correlated with the concentration of sorafenib in the skin. Our results suggested the involvement of the TGF-β1/Smads signaling pathway in the skin reaction induced by MKIs.

Cited by 3 publications

References 20 publications

In vivo assessment of the drug interaction between sorafenib and paracetamol in rats

In vivo assessment of the drug interaction between sorafenib and paracetamol in rats

Solute Carrier Transportome in Chemotherapy-Induced Adverse Drug Reactions

Sorafenib inhibits ovarian cancer cell proliferation and mobility and induces radiosensitivity by targeting the tumor cell epithelial–mesenchymal transition

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